Universiẗat, Diss., 2000--Wuppertal.

Universiẗat, Diss., 2003--Düsseldorf.

Universiẗat, Diss., 2000--Dortmund. / Dateiformat: PDF.

Techn. Hochsch., Diss., 2002--Aachen.

Techn. Hochsch., Diss., 2003--Aachen.

Les sécoiridoïdes sont des monoterpènes hautement fonctionnalisés utilisés comme matières premières chirales renouvelables en hémisynthèse, lorsqu’ils sont abondants au sein des végétaux. Un nouveau procédé vert d’extraction aqueuse et de purification utilisant des résines et la chromatographie de partage centrifuge a permis l’isolement de plus de 100 g d’oleuropéine des feuilles d’Olea europaea et d’une douzaine de grammes de sécologanoside et de sweroside des feuilles de Lonicera tatarica. L’ouverture de la lactone du perpivaloylsweroside a été effectuée en milieu organique apolaire par le TMSONa. Cette réaction a été étendue à 8 lactones commerciales et 5 lactones de sécoiridoïdes. Une approche mécanistique de cette nouvelle réaction a été établie sur la γ-butyrolactone à l’aide d’une étude cinétique. Cette réaction a été utilisée pour la conversion du sweroside en sécologanoside en quatre étapes. Cette approche séquentielle a été appliquée avec succès sur les dérivés du sweroside. Quatre nouveaux analogues du sécologanoside et 9 synthons chiraux originaux ont ainsi été isolés. De plus l’étude de la réactivité de l’oleuropéine a permis l’obtention de 4 nouveaux synthons et un analogue isomérique du sécologanoside. Ces analogues de sécologanoside sont précurseurs de nouveaux alcaloïdes indolo-monoterpèniques. Enfin la double liaison exocyclique du sweroside a pu être sélectivement ozonolysée et épimérisée pour conduire à la formation d’un synthon clé pour la synthèse de diterpènes cytotoxiques marins de types xénicanes. / Secoiridoids are highly functionalized monoterpenes and can be used as renewable raw materials in semi-synthesis when they are abundant in plants. A new green process of water extraction and purification by resins or centrifugal partition chromatography allowed the isolation of more than 100 g of oleuropein from Olea europaea leaves and a dozen of grams of secologanin and sweroside from Lonicera tatarica leaves.The lactone ring opening of perpivaloylsweroside was achieved in apolar solvents by TMSONa. The scope of this reaction was extended to 8 commercial lactones and 5 secoiridoid lactones. A mechanistic approach of this new reaction on γ-butyrolactone was established by kinetic studies. This reaction was used for the conversion of perpivaloylsweroside into secologanin, in four steps. This approach was successfully applied on sweroside derivatives. Four enantiopure secologanin analogs and 9 chiral synthons were isolated. Furthermore the reactivity study of oleuropein afforded 3 new synthons and one isomeric analog of secologanin. These secologanin analogs are synthetic precursors of new indolo-monoterpenic alkaloids. Finally the exocyclic double bond of sweroside was selectively ozonolyzed and epimerized to yield a key synthon for the synthesis of cytotoxic marine diterpenes xenicans.

Submitted by Jaqueline Silva (jtas29@gmail.com) on 2014-09-19T19:05:02Z No. of bitstreams: 2 Silva, Cameron-2014-dissertação.pdf: 4685861 bytes, checksum: 35a25c14813b0206d3d9c8fa6c8bfdaf (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-09-19T19:05:31Z (GMT) No. of bitstreams: 2 Silva, Cameron-2014-dissertação.pdf: 4685861 bytes, checksum: 35a25c14813b0206d3d9c8fa6c8bfdaf (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-09-19T19:05:31Z (GMT). No. of bitstreams: 2 Silva, Cameron-2014-dissertação.pdf: 4685861 bytes, checksum: 35a25c14813b0206d3d9c8fa6c8bfdaf (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-03-06 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Co-crystallization of active pharmaceutical ingredients has been widely studied lately in order to improve the solid state features of such compounds, for example solubility, and also to protect the intellectual property of such compounds. Multicomponent molecular crystals can be prepared from both supramolecular synthon and screening approaches, which involve the variation of crystallization conditions. In this way, molecular crystal engineering is a strategy to improve solid state properties of drugs related to their efficacies. One branch of the lamivudine crystal engineering deals with its protonable pyrimidine-based nitrogen being a recipe of crystallization with carboxylic acids. Such strategy has yielded several pharmaceutical co-crystals and salts of APIs that have lamivudine-like heterocyclic nitrogens by choosing suitable carboxylic acids as a salt/co-crystal former. In this context and in relation to the drug antiretroviral nucleoside reverse transcriptase inhibitor lamivudine, four new crystalline phases thereof were prepared, their crystal structures were determined by X-ray diffraction by single crystal, and their solubility in water were measured. For the first time it was observed an in-plane pairing of lamivudine with the carboxylate and carboxyl functionalities of a same salt former unit giving rise to a trimer and a tetramer in the structures of lamivudine hydrogen phthalate hemihydrate and lamivudine hydrogen 4,5-dichlorophthalate, respectively. Besides, a new synthon have been found in the first salt. All lamivudine salts were less soluble than the lamivudine form II (free base). The unexpected heterosynthon can be related to the slightly higher solubility of lamivudine hydrogen 4,5-dichlorophthalate when compared to the other salts prepared in this study. / Co-cristalização de insumos farmacêuticos ativos tem sido largamente estudada ultimamente a fim de melhorar as propriedades do estado sólido, como, por exemplo, a solubilidade, e também manter a propriedade intelectual de tais compostos. Cristais moleculares multicomponentes podem ser preparados a partir da abordagem de sínton supramolecular e também através de métodos sistemáticos de investigação laboratorial, o que envolve a variação de condições de cristalização dos fármacos. Neste sentido, a engenharia de cristais moleculares é uma estratégia para aperfeiçoar as propriedades de estado sólido relacionadas às eficácias dos fármacos. Um ramo da engenharia de cristais de lamivudina lida com sua base nitrogenada pirimidina, a qual pode ser protonada, sendo assim um alvo de co-cristalização com ácidos carboxílicos. Tal estratégia tem rendido vários co-cristais e sais de insumos farmacêuticos ativos que possuem nitrogênio heterocíclico como a lamivudina pela escolha adequada de ácidos carboxílicos como um formador de sal/co-cristal. Nesse contexto, e com relação ao fármaco antirretroviral inibidor nucleosídeo de transcriptase reversa, a saber, lamivudina, quatro novas fases cristalinas foram preparadas, suas estruturas cristalinas foram elucidadas por difração de raios X por monocristal, e suas solubilidades em água foram aferidas. Nesse estudo, pela primeira vez foi observado um duplo pareamento da droga com ambas as funcionalidades ácidas do contra-íon originando uma tríade e um tetrâmero planar nas estruturas de biftalato de lamivudina hemidratado e 4,5-diclorohidrogenoftalado de lamivudina, respectivamente. Além disso, um novo sínton foi encontrado no primeiro sal. Todos eles foram menos solúvel do que a forma II da lamivudina (base livre). O inesperado heterosínton pôde ser correlacionado com a solubilidade ligeiramente maior do 4,5-diclorobiftalato de lamivudina quando comparado com os demais sais preparados.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-12-18T12:04:06Z No. of bitstreams: 2 Tese - Cameron Capeletti da Silva - 2017.pdf: 3293032 bytes, checksum: 714ecd70f3ac6d81018c08280d885007 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-12-18T12:04:37Z (GMT) No. of bitstreams: 2 Tese - Cameron Capeletti da Silva - 2017.pdf: 3293032 bytes, checksum: 714ecd70f3ac6d81018c08280d885007 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-12-18T12:04:37Z (GMT). No. of bitstreams: 2 Tese - Cameron Capeletti da Silva - 2017.pdf: 3293032 bytes, checksum: 714ecd70f3ac6d81018c08280d885007 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-12-13 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / A branch of lamivudine crystal engineering deals with its protonable pyrimidine-based nitrogen being a recipe of crystallization with acids. In this context and in relation to the drug lamivudine, ten new crystalline phases were prepared and their crystal structures were elucidated by single crystal X-ray diffraction. In addition, two of them were also characterized by infrared spectroscopy (IR) and other three were characterized by TG and DSC thermal analysis. Thus, this study shows an interesting example of chiral recognition even without chiral resolution. Lamivudine (R)-mandelate and (S)-mandelic acid cocrystal of lamivudine (R)-mandelate trihydrate showed the enantiopreference between lamivudine cation and the (R)-mandelandelate anion in both salt and cocrystal of salt phases through the robust synthon 2-aminopyridine-carboxylate. The present study shows how two solid forms of lamivudine with mandelic acid were used as a model to distinguish between the nature of a salt or cocrystal of salt. This happened because specific information obtained from IR spectra allowed the identification of ionized and neutral forms of mandelic acid directly in the spectrum of the cocrystal of salt. Furthermore, the formation of crystalline forms of lamivudine resembling a DNA structure was investigated due to its great structural value. After crystallization experiments three crystalline structures of lamivudine that mimics DNA structure were obtained and named as lamivudine duplex IV, V and VI, respectively. In the duplex IV of lamivudine the counterions are responsible for opening the two strands due to their hydrogen bonding pattern. The theoretical approach has shown that there is not an energetic tendency regarding the formation of lamivudine duplex with aliphatic organic acids or lamivudinium salts with aromatic acid. Thus, the preference of lamivudine in the assembly of double-helix structures with aliphatic organic acids rather than aromatic acids has been rationalized based on the amount of acid used during the synthesis. In addition, four other salts were also prepared by crystallizing lamivudine with the L-tartaric, sulfuric and perchloric acids, where the two-point synthon described by the graph set R22(8) prevailed. On the other hand, in the structure of lamivudine perchlorate monohydrate neither the two-point synthon nor the three-point one was observed. Finally, the first anhydrous polymorph of lamivudine was reported. This new polymorphic phase of lamivudine is anhydrous as well as form II. In addition to being a new solid phase of alleged commercial interest, the polymorphic form IV of lamivudine also reinforces the importance of performing an extensive screening of the crystallization conditions of new crystalline modifications of active pharmaceutical ingredients. / Um ramo da engenharia de cristais de lamivudina lida com sua base nitrogenada pirimidina, a qual pode ser protonada, sendo assim um alvo de cristalização com ácidos. Nesse contexto, e com relação ao fármaco lamivudina, dez novas fases cristalinas foram preparadas e suas estruturas cristalinas foram elucidadas por difração de raios X por monocristal. Além disso, duas delas também foram caracterizadas por espectroscopia no infravermelho (IV) e outras três foram caracterizadas termicamente por TG e DSC. Desse modo, esse estudo mostra o interessante exemplo de reconhecimento quiral mesmo sem resolução quiral. O (R)-mandelato de lamivudina e o co-cristal (S)-mandélico de (R)-mandelato de lamivudina trihidratado revelaram a enantiopreferência da conexão entre o cátion (lamivudina)+ e o ânion (R)-mandelato- em ambas fases de sal e co-cristal de sal através do sínton robusto de dois pontos 2-aminopiridina-carboxilato. O presente estudo mostra que as duas formas sólidas de lamivudina com ácido mandélico foram utilizadas como modelo para distinguir entre a natureza de um co-cristal de sal e de um sal. Isso porque informações específicas obtidas dos espectros de IV tornaram possível identificar ambas as formas ionizadas e neutra do ácido mandélico diretamente no espectro do co-cristal de sal. Ainda, investigou-se a formação de formas cristalinas de lamivudina que se assemelham a estrutura de DNA devido a seu grande valor estrutural. Após os experimentos de cristalização foram obtidas três estruturas cristalinas de lamivudina semelhantes a estrutura de DNA denominadas de dupla hélice de lamivudina IV, V e VI. Na dupla hélice de lamivudina IV os contra-íons são responsáveis pela abertura da dupla fita devido ao seu padrão de ligação de hidrogênio. A abordagem teórica mostrou que não há uma tendência energética com respeito a formação de duplex de lamivudina com ácidos orgânicos alifáticos ou de sais de lamivudina com ácidos aromáticos. Desse modo, a preferência da lamivudina em montar estruturas cristalinas de dupla hélice com ácidos orgânicos alifáticos ao invés de ácidos aromáticos foi racionalizada com base na quantidade de ácido usada durante a síntese. Além disso, também foram preparados outros quatro sais ao cristalizar lamivudina com os ácidos L-tartárico, sulfúrico e perclórico, onde o sínton de dois pontos descrito pelo conjunto gráfico R22(8) prevaleceu. Por outro lado, na estrutura do perclorato de lamivudina monohidratado nem o sínton de dois pontos e nem o de três pontos foram observados. Por fim, o primeiro polimorfo anidro de lamivudina foi reportado. Essa nova fase polimórfica de lamivudina é anidra assim como a forma II. Além de ser uma nova fase sólida de suposto interesse comercial, a forma polimórfica IV de lamivudina também reforça a importância de se realizar uma varredura extensiva das condições de cristalização de novas modificações cristalinas de insumos farmacêuticos ativos.

The thesis entitled "SYNTHETIC INVESTIGATIONS IN TERPENOIDS AND STEROIDS" consists of 3 Chapters Chapter-I deals with the synthetic studies on the hexacyclic nortriterpene Pfaffic acid 1, and is divided into two sections. Section-I begins with a brief introduction to Pfaffic acid 1, a naturally occurring hexacyclic nortriterpene, in particular to its isolation, structural elucidation and antitumor activity. The antitumor activities of the Pfafosides A, B, C, D, E and F, the glycosides of pfaffic acid 1, isolated from the same plant is also described. The discussion presents the synthetic strategy developed to construct the AB ring system along with the results of the attempted synthesis of DEF ring of Pfaffic acid 1. The retrosynthetic analysis of 1 identified the key intermediates as AB synthon 2, and the DEF synthon 3, Regioselective hydride reduction of Wieland-Mischer ketone, followed by hydroxyl protection and Woodward methylation gave the dimethylated compound 4 Deprotection of the hydroxyl group and reduction of the carbonyl followed by acetylation resulted in the diacetate 5 Oxidation of the diacetate 5 with PDC-/BuOOH-celite system followed by lithium-liquid ammonia reduction yielded the saturated keto diol 6, which on dehydration and subsequent acetylation afforded the enone acetate 2, which formed the AB ring of Pfaffic acid 1 The synthetic studies towards the construction of DEF rings of Pfaffic acid commenced with the preparation of the indane methanol 7 The alcohol 7 was synthesized starting from 5-methoxyindan-l-one Thus 5-methoxyindanone was converted into the hydroxymethyl compound 8 by Wittig reaction and subsequent hydroboration Swern oxidation of 7, followed by methylation and reduction resulted in the indane methanol 7 Lithium-ammonia reduction of 7 gave a dihydrocompound, which on hydrolysis with oxalic acid gave the isomeric enones 9 and 10 in 1 1 ratio On the other hand, hydrolysis of the dihydrocompound with 5N HC1 in methanol afforded the isomers 9 and 10 in 85 15 ratio Addition of KCN to the isomeric enone mixture (85 15) resulted in the lactone 11 in 60% yield.The formation of the lactone 11 clearly established that the major isomer of the mixture has the angular hydrogen and hydroxymethyl group in as orientation as represented in 9, but unfortunately this geometry is unfavorable for the construction of the DEF ring of Pfaffic acid Similar Birch reduction of the alcohol 8 gave the corresponding dihydrocompound, which on hydrolysis with 5N HC1 in methanol afforded the isomeric alcohols 12 and 13 in 92 8 ratio Hydrogenation of the mixture followed by tosylation yielded the tosylates 14 and 15 in the same ratio Attempted intramolecular cyclisation of the tosylate mixture with different bases failed to yield any tricyclic compound, indicating that the major isomer has the unfavorable geometry for intramolecular alkylation. The origin of stereoselectivity during the hydrolysis of the enol-ether leading to the formation of the isomers 9 and 12 in major amount, was found to be due to a novel hydroxyl directed protonataon as represented in 16 Section-ll describes a novel oxidative C-C bond cleavage reaction with chromium reagents The alcohol 8 when oxidized with a variety of chromium reagents gave 5-methoxyindan-1-one in good yields. The mechanism of this reaction seems to go via the enol 17, which undergoes C-C bond cleavage to afford 5-methoxyindan-l-one. A number of 1-hydroxymethyl indanes 18 and 1-hydroxymethyl tetralins 19 were synthesized and their oxidation with PCC and PDC was examined In all these cases a smooth C-C cleavage was observed resulting in the respective aryl ketones Chapter-II deals with the synthetic investigations on the construction of the tricyclic ACE synthon 20, a potential intermediate for the synthesis of A-ring aromatic steroids, and is divided into two sections. Section-] describes the literature pertaining to the synthetic approaches towards A-ring aromatic steroids, with the emphasis being a critical analysis of the methodologies developed for estrone. Section-ll is divided into two parts Part-I presents the results of the synthetic studies on the construction of the tricyclic ACE synthon 20 The section starts with a need to develop a convenient methodology for the synthesis of aryltetralin 21 The new process developed for the synthesis of 21 involved a one pot Friedel-Crafts arylation of the 7-methoxy-l-tetralol 22 with the phenol to afford the aryltetralin 21 in high yield This methodology was extended to the synthesis of a number of aryl tetralins 22 to show the generality of this reaction Benzylic oxidation of the acetate of 21, afforded the aryl ketone, which on hydrolysis followed by benzylation with yielded the tetralone 24 Wittig olefination of the tetralone 24, followed by hydroboration afforded the hydroxymethyl compound 25 Swern oxidation of the hydroxymethyl compound 25 and subsequent methylation and sodium borohydride reduction gave the aryltetralin 26 along with its isomer 27 Both these isomers were separated by column chromatography over silica gel and subjected to hydrogenation to afford isomeric diols 28 and 29 Birch reduction of 28 afforded the dihydrocompound, which on acid hydrolysis resulted in a mixture of compounds consisting of 30, 31, 32, and 33 The diastereomeric isomers 30 and 31 were separated together from the other set of diastereomeric isomers 32 and 33 by column chromatography over silicagel, but the individual diastereomers could not be separated On the other hand hydrolysis of the dihydrocompound for a longer period (24 h) yielded the compound 32 as a single isomer along with the mixture 30 and 31 Part-II describes a new synthetic methodology for the construction of bicyclo[3 2 2]nonanes, During the preparation of the aryltetralin derivative 28, a hitherto unknown double Friedel-Crafts reaction, leading to the formation of bicyclo[3.2 2]nonane derivative was observed The diol 35 on treatment with phenol and A1C1, unexpectedly underwent a novel double Friedel-Crafts reaction to afford the bicyclo[3 2 2]nonane derivative 36 The mechanism of this reaction was found to go via the aryl tetralin 28 and the generality of this reaction was demonstrated by the synthesis of different aryltetralin derivatives 37, by reacting the diol with various arylating agents Chapter-III deals with the direct conversion of 130-alkylgona tetraenes into 19-nortestosterone derivatives Birch reduction of 8-dehydroestradiol-3-methyl ether 38 and 9(11)-dehydroestradiol-3-methyl ether 39 followed by acid hydrolysis results in a mixture of 19-nortestosterone 40 and retro-19- nortestosterone 41 in varying amounts However, reduction of the acetates of 38 and 39 with sodium or lithium, in the presence of aniline affords exclusively 19-nortestosterone 40 Similarly the acetate of 42 was converted to 18-homo-19-nortestosterone 43

Crystal engineering underlies the essence of natural affiliation between the molecule on the one side and the crystal as a supramolecular assembly on the other. Molecular recognition is the fundamental cause for this efficient transformation and if we consider the crystal as a supramolecular entity then it is not at all difficult to conceive crystallization as an outstanding example of molecular recognition. In general, organic compounds often facilitate closed packed crystal structures as described by A. I. Kitaigorodskii in the form of the close packing principle but based on chemical features, there is still a small window to understand, to rationalize and to fashion new crystal structures. Extending the chemical viewpoint as first proposed by J. M. Robertson, the supramolecular synthon model as a descriptor of collective crystal structures has been invoked that enables one to trail the molecular behaviour from an entropy dominated situation in solution to an enthalpy driven progression in the solid state. After 20 years, the concept of the supramolecular synthon has stood the test of time because of its simplicity and effectiveness towards the implementation in complex crystal structures and has led the scientific community to further handle complex and interesting ideas in structural chemistry and supramolecular synthesis. The complexity of dynamic and progressive behavior of molecules during crystallization may be understood by the analogous argument of protein folding; both these complex phenomena decode the emergence of multiple metastable forms before the final structures are attained. These intermediate kinetically driven species may be high energy polymorphs and pseudopolymorphs of the compound in question or semicompact random globules for proteins. Understanding the role of these species in their respective processes is of critical importance in elucidating mechanisms. As an alternative approach, crystal structure prediction (CSP) is also of fundamental importance in the context of understanding the crystallization process. All energy based computational methods of CSP address this problem by scanning the multi-dimensional energy hypersurface. This is performed by computing lattice energy changes with respect to parameters like unit cell dimensions, space group symmetry and the positional coordinates of atoms in the asymmetric unit. Further, the computational prediction of the crystal structure of an organic compound results in several choices, and it is possible that a collection of some of these when taken together forms a pattern that mimics the course of the crystallization process very much in the manner that structure correlation mimics covalent bond breaking and making. With all these developments, one is truly at the stage today when any experimental or computed crystal structure is just that, a crystal structure of the molecule in question and it is part of a complex and dynamic structural space which may include a part of the supramolecular reaction trajectory for crystallization itself. Accordingly, this thesis emphasizes the importance of kinetic events during crystallization and proposes some strategies to access the inaccessible domains of this structural space of a given compound. I have exploited the supramolecular synthon model to understand the kinetics of the crystallization process and have further extended this understanding towards the isolation of stoichiometric ternary solids. The synthon model also helps one to provide a logical step to explore these remote domains of the complex hyperenergy surface that have collectively been termed as the crystal structure landscape of the compound in question. The precise descriptions of the chapters are mentioned below. Chapter 2 describes fluorosubstitution as a unique chemical probe to explore the high energy crystal structures of benzoic acid in ambient conditions. This landscape exploration of benzoic acid is based on the robust (kinetically favoured) supramolecular homosynthon as well as consistent fluorosubstitution in native compound. This analysis is also supported by synthon based crystal structure prediction which is one of the best ways of monitoring high energy virtual crystal structures. Chapter 3 extends the idea of landscape exploration towards multicomponent systems. The incorporation of an additional compound during crystallization facilitates even complex kinetic environments but using fluorosubstitution as a chemical probe, it again helps to analyse the high energy virtual domains of the given multicomponent system. Similar to chapter 2, the landscape exploration of multicomponent system is also based on the robust (kinetically favoured) supramolecular heterosynthon as well as consistent fluorosubstitution in the native multicomponent system. Chapter 4 emphasizes the importance of synthon modularity as a chemical probe to traverse in the crystal structure landscape of the given multicomponent system. Here, I have quantified the role of the definitive synthon, by using the supramolecular synthon based fragment approach (SBFA), in the emergence of polymorphism in cocrystals. In latter part of this chapter, I utilized this collective kinetic information in order to realize the combinatorial nature of the crystallization process and showed the complex combinatorial synthesis of ternary solids which itself is considered to be an arduous exercise. Chapter 5 discusses the importance of kinetic information which were fetched from the corresponding multicomponent landscapes and were further utilized for combinatorial synthesis of ternary solids. Although the combinatorial idea is well established in solution, this chapter highlights the first experimental evidence of this idea in the solid state and shows preferred amplification of certain supramolecular synthons from corresponding libraries in the supersaturated crystallizing medium. Chapter 6 extends the combinatorial idea of crystallization even further by using highly flexible organic compounds that collectively provide larger structural space during crystallization. Using the delicate kinetic information about the molecular and supramolecular features, this chapter describes the preferential selection of molecular conformation and supramolecular synthons from the supersaturated solution during the molecule→crystal pathway. In summary, the idea of the crystal structure landscape provides an extended interpretation about some of the complex ideas namely, crystal energy landscape and polymorphism in modern crystal engineering. The crystallization of an organic compound often depends upon intrinsic chemical features and accordingly one selects optimized crystallization routes in the corresponding landscape through decisive experimental conditions. As a final note, the idea of the crystal structure landscape enables one to (at least qualitatively) understand the importance of crystallization kinetics which is understandably a difficult task.