Amino aldehydes are important building blocks in organic synthesis. However, due to the innate propensity for condensation to occur upon combination of aldehydes and amines, uprotected amino aldehydes are unstable. One exception to this is the existence of dimeric aziridine aldehydes. We have shown that the enhanced stability observed with these unprotected aziridine aldehydes is due to their dimeric nature. In addition, we have shown that reversible dimer dissociation plays a key role in the kinetics and stereoselectivity of subsequent reactions. Reductive amination with the unprotected amino aldehyde dimers occurs without double addition or epimerization. The resulting aziridine conjugates were used towards a convergent synthesis of aminomethylene peptidomimetics, by aziridine ring opening with C-terminal peptide thioacids. We have shown that we can also utilize the aziridine aldehydes towards the assembly of branched peptides.

Amino aldehydes are important building blocks in organic synthesis. However, due to the innate propensity for condensation to occur upon combination of aldehydes and amines, uprotected amino aldehydes are unstable. One exception to this is the existence of dimeric aziridine aldehydes. We have shown that the enhanced stability observed with these unprotected aziridine aldehydes is due to their dimeric nature. In addition, we have shown that reversible dimer dissociation plays a key role in the kinetics and stereoselectivity of subsequent reactions. Reductive amination with the unprotected amino aldehyde dimers occurs without double addition or epimerization. The resulting aziridine conjugates were used towards a convergent synthesis of aminomethylene peptidomimetics, by aziridine ring opening with C-terminal peptide thioacids. We have shown that we can also utilize the aziridine aldehydes towards the assembly of branched peptides.

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

The flavour or fragrance of Basmati rice is associated with the presence of 2-acetyl-1- pyrroline. This work shows that a gene with homology to betaine aldehyde dehydrogenase (BAD) has significant polymorphisms in the coding region of fragrant genotypes relative to non fragrant genotypes. Accumulation of 2-acetyl-1-pyrroline in fragrant rice genotypes may be explained by the presence of mutations resulting in loss of function of the fgr gene product. The fgr gene corresponds to the gene encoding BAD2 in rice while BAD1 is encoded by a gene on chromosome 4. Development of an allele specific amplification (ASA) based around the deletion in the gene encoding BAD2 allows, perfect, simple and low cost discrimination between fragrant and non-fragrant rice varieties and identifies homozygous fragrant, homozygous non-fragrant and heterozygous non-fragrant individuals in a population segregating for fragrance. The cDNAs transcribed from rice chromosomes 4 and 8, each encoding an enzyme with homology to betaine aldehyde dehydrogenase were cloned and expressed in E. coli. The enzyme responsible for fragrance, encoded from chromosome 8, had optimum activity at pH 10, showed low affinity towards betaine aldehyde (bet-ald) with Km value of approximately 63ìM but a higher affinity towards -aminobutyraldehyde (GABald) with a Km value of approximately 9ìM. The enzyme encoded from chromosome 4 had optimum activity at pH 9.5 and showed generally lower affinity towards most substrates compared to the enzyme encoded from chromosome 8, substrate specificities suggest that the enzymes have higher specificity to aminoaldehydes and as such both should be renamed as an aminoaldehyde dehydrogenase (AAD). The inactivation of AAD2 (BAD2) in fragrant rice varieties likely leads to accumulation of its main substrate GABald which then cyclises to 1-pyrroline the immediate precursor of 2AP.

The flavour or fragrance of Basmati rice is associated with the presence of 2-acetyl-1- pyrroline. This work shows that a gene with homology to betaine aldehyde dehydrogenase (BAD) has significant polymorphisms in the coding region of fragrant genotypes relative to non fragrant genotypes. Accumulation of 2-acetyl-1-pyrroline in fragrant rice genotypes may be explained by the presence of mutations resulting in loss of function of the fgr gene product. The fgr gene corresponds to the gene encoding BAD2 in rice while BAD1 is encoded by a gene on chromosome 4. Development of an allele specific amplification (ASA) based around the deletion in the gene encoding BAD2 allows, perfect, simple and low cost discrimination between fragrant and non-fragrant rice varieties and identifies homozygous fragrant, homozygous non-fragrant and heterozygous non-fragrant individuals in a population segregating for fragrance. The cDNAs transcribed from rice chromosomes 4 and 8, each encoding an enzyme with homology to betaine aldehyde dehydrogenase were cloned and expressed in E. coli. The enzyme responsible for fragrance, encoded from chromosome 8, had optimum activity at pH 10, showed low affinity towards betaine aldehyde (bet-ald) with Km value of approximately 63ìM but a higher affinity towards -aminobutyraldehyde (GABald) with a Km value of approximately 9ìM. The enzyme encoded from chromosome 4 had optimum activity at pH 9.5 and showed generally lower affinity towards most substrates compared to the enzyme encoded from chromosome 8, substrate specificities suggest that the enzymes have higher specificity to aminoaldehydes and as such both should be renamed as an aminoaldehyde dehydrogenase (AAD). The inactivation of AAD2 (BAD2) in fragrant rice varieties likely leads to accumulation of its main substrate GABald which then cyclises to 1-pyrroline the immediate precursor of 2AP.

Pour développer de nouveaux outils synthétiques, nous avons élaboré des variantes de la réaction de Petasis. L’utilisation des α-amino aldéhydes dans la réaction de Petasis a permis de synthétiser des diamines chirales avec une diastéréosélectivité totale. La réaction a donnée de bons résultats avec différents groupements protecteurs de l’amine (sulfonamide, carbamate, amide). Cependant au cours de la réaction, les amino aldéhydes s’épimérisent et l’excès énantiomérique des diamines préparées est donc faible (30%). La réaction de Petasis a été associée à la réaction de Diels-Alder dans un procédé domino pour aboutir à l’obtention de composés de type hexahydroisoindole. La réaction domino est complètement diastéréosélective et les molécules sont obtenues de manière énantiopure. Un second procédé domino, utilisant une réaction de métathèse croisée suivie d’une addition 1,4 intramoléculaire, a permis d’obtenir des composés possédant un motif morpholine de manière diastéréosélective. Une version intramoléculaire de la réaction de Petasis a été mise au point dans le but d’obtenir des carbocycles à six chainons. Cette réaction a permis de préparer la (+)-conduramine C-4 en peu d’étapes. La cyclisation a montré une diastéréosélectivité surprenante puisque la configuration entre l’amine nouvellement formée et l’alcool est trans. Cette configuration est opposée à celle obtenue dans la version intermoléculaire. / To develop new synthetic tools, we developed variants of the Petasis reaction. The use of α-amino aldehydes in the Petasis reaction allowed to synthesize chiral diamines with a total diastereoselectivity. The reaction gave good results with different protective groups of the amine (sulfonamide, carbamate, amide). However, during the reaction, the amino aldehydes are epimerized and the enantiomeric excess of the prepared diamines is low (30%). The Petasis reaction was associated with the Diels-Alder reaction in a domino process to achieve the preparation of hexahydroisoindole type compounds. The domino reaction is completely diastereoselective and the molecules are obtained as enantiopure. A second domino process, using a cross-metathesis reaction followed by an intramolecular 1,4-addition, yielded compounds with a morpholine moiety in a diastereoselective manner. Intramolecular version of the Petasis reaction was developed in order to obtain carbon-six-membered rings. This reaction led to the preparation of (+)-conduramine C-4 in few steps. The cyclization has shown a surprising diastereoselectivity since the configuration between the newly formed amine and alcohol is trans. This configuration is opposite to the one obtained in the intermolecular versions.