Several bioactive thiazolopyridoacridines of marine origin have been synthesized. Kuanoniamine D was synthesized in 18 steps from cyclohexanedione mono-ethyleneketal in 7.3% overall yield. The most potent member of the family, dercitin, was also synthesized from cyclohexanedione mono-ethyleneketal in 18 steps and 7.2% overall yield. Nordercitin was produced from the same starting material in 16 steps and 9.3% overall yield. This work also confirms the revision of the controversial structural assignments of dercitin and nordercitin. These efficient total syntheses include a new pyridine-forming sequence and a photochemical nitrene insertion as crucial steps. A novel approach to the streptonigrinoids, a family of potent antitumor antibiotics, is also described. An efficient formal total synthesis of the methyl ester of lavendamycin has been completed to demonstrate the usefulness of this approach. Key steps include a new pyridine-forming sequence and a thermolytic nitrene insertion to form a $\beta$-carboline. This formal synthesis is several steps shorter and an order of magnitude more productive than previously reported synthetic approaches.

A novel method for the synthesis of complex 1,2 amino alcohols of syn stereochemistry has been achieved via the condensation of $\gamma$-oxygenated allylstannanes with activated imines. The imines are activated by an N-aryl group, and boron trifluoride etherate. The N-aryl functionality serves to delocalize the negative charge developing on nitrogen. Imines with both N-aryl/C-aryl and N-aryl/C-aliphatic functionality have been prepared, and condensed with various allylstannanes. Previously unknown N-aryl/C-aliphatic imines have been synthesized for the first time, using a modified Wadsworth-Emmons reaction. The syn stereochemistry of the reaction has been proven by NOEDS of the oxazolone derivatives of the condensation products. The 4-carbomethoxyphenyl (4-CMP) group has been developed as an excellent activating group for the imine. The facile removal of this functionality has been demonstrated by use of the Birch reduction.

Optically pure mitomycin C was synthesized in 28 steps and 5% overall yield from 2,6-dimethoxytoluene. The route followed was a variation upon previous work in our laboratories and the asymmetry was achieved by the resolution of racemic mitomycin A, an advanced intermediate. Our efforts at finding a new route to an intermediate in the synthesis of FR900482, are also described here. The key step was the cyclization of an epoxy-acetamide under basic conditions to form an eight-membered lactam.

The stereochemical outcomes and trends of catalysis of hydroboration of alkenes by catecholborane using rhodium(I) catalysts is examined. For 1,2-chirality transfer in simple allylic alcohol derivatives with aliphatic substituents on the chiral center the syn diastereoisomer is formed preferentially, this result is stereocomplementary to the stereoselectivities observed in reaction with hindered alkyl borane reagents. Syn diastereoselectivity, in the catalyzed reaction, is found to increase with increasing electron withdrawing power of the substituent on oxygen and with its steric bulk. The observed stereochemical outcome of the catalyzed reactions is postulated to be the result of binding of the substrate to the low valent metal catalyst in such a way that it behaves as the best ligand for a transition metal, i.e. such that the $\pi$* of the alkene lowered by perturbation with the lowest energy $\sigma$* of a bond on the chiral center (electronic effect). This occurs when bond to the oxygen substituent is aligned with the lobes of the $\pi$* orbital. Steric interactions dictate that the metal bonds opposite the alcohol substituent, and the larger this group is, the larger its preference to occupy this position (steric effect). N-(benzyltosyl) allyl amines were subjected to catalyzed and uncatalyzed hydroboration conditions. The catalyzed reactions give syn selectivity as anticipated. However 9-BBN also gives syn products preferentially which was not expected from analogy of the behavior of this reagent with allylic alcohol derivatives. Borane-THF complex gives consistantly high anti selectivity with these substrates. Transfer of chirality from a monochiral rhodium catalyst to several simple prochiral alkenes is described. The efficiency of this enantioselective hydroboration process is strongly dependant on the type monochiral bisphosphine used to form the catalyst. A new class of monochiral bisphosphine which contains stereogenic phosphorus centers, and a chiral backbone linking them, were synthesized by alkylation of unsymmetrically substituted phosphide ions with 1,4-Ditosyl-2,3-O-isopropylidene-L-threitol. Separation of the resulting epimeric (at phosphorus) compounds was achieved by flash chromatography of molybdenum carbonyl complexes. Decomplexation to give pure diastereoisomers is carried by treatment with sodium naphthenalide.

A novel method for the enantioselective synthesis of nitrogen containing compounds has been achieved. The oxidative rearrangement of N-acyl 2-furylamines, termed the Aza-Achmatowicz rearrangement, generates a product with a high density of differentiable functionalities. This characteristic of the product makes it an excellent building block for the synthesis of nitrogenous substances of biomedical interest. Optically pure building blocks are also available via the Aza-Achmatowicz rearrangement. The generation of chirality in the starting furyl derivative is obtained by a simple, inexpensive chemoenzymatic method utilizing papain. The chemical reactivity of these heterocycles has been thoroughly explored, and utilized in the synthesis of (+)-desoxoprosopinine, deoxyazasaccharides, izidinie alkaloid systems, $\beta$-lactams, and unusual amino acids.

Formation of the skeleton of renieramycin A was achieved through sequential condensations of piperazinedione and substituted benzaldehydes. One of the key reactions of this synthesis, oxidation of benzylic position, produced hydroxylated compound 62 (see p. 22 in dissertation for illustration). Further elaboration of 62 has resulted in N-methyl 65 (p. 22), an important precursor to renieramycin A.

A new benzannulation reaction was discovered. The reaction involves intramolecular attack into a carbon-carbon triple-bond by the alpha position of a beta-ketoester under acidic conditions. Four different beta-ketoester starting materials were prepared and were successfully cyclized. This benzannulation methodology should provide a convenient pathway for forming aromatic products to be used as building blocks in the syntheses of anti-tumor antibiotics.

Investigations of the biosynthesis of the antitumor antibiotic sparsomycin (1) by Streptomyces sparsogenes have been carried out. Incorporation studies employing ($\sp{13}$C)-labeled precursors have shown that the monoxodithioacetal moiety (6) of the antibiotic arises from the step-wise introduction of a thiomethyl group into the S-methyl group of S-methyl-D-cysteine. The methyl group of (6) has its origin in the methyl group of L-methionine, but an experiment utilizing (methyl-$\sp3$H,$\sp{35}$S) -L-methionine has demonstrated that intact incorporation of the thiomethyl group of this precursor does not occur. The results of feeding experiments with ($\sp{13}$C)- and ($\sp2$H)-labeled forms of tryptophan have indicated that the uracil moiety (7) of sparsomycin is derived from the indole nucleus of tryptophan via aromatic ring cleavage followed by recyclization. Preliminary evidence for the intermediacy of N-formyl-anthranilic acid in the conversion of tryptophan to sparsomycin has been obtained.

The biosynthesis of the antifungal, antiviral antiobiotic, sinefungin (1), produced by Streptomyces griseolus has been investigated. Precursor incorporation studies using (U-$\sp{14}$C), (5-$\sp3$H), (5-$\sp{13}$C) and (5-$\sp{13}$C, 5-$\sp{15}$N)-ornithine have shown that carbons 6$\sp\prime$-10$\sp\prime$ were derived from the intact incorporation of ornithine with retention of the C-5 nitrogen and with the loss of one of the protons from C-5 of ornithine. The results of the feeding experiments of ($\sp{14}$C) and ($\sp3$H) labelled adenosine have indicated that the adenine moiety of adenosine was incorporated intact. Administration of adenosine labelled on the ribose moiety indicated that adenosine was incorporated into sinefungin with 50% loss of protons from C-5$\sp\prime$ of adenosine.

Tantazole B is a newly isolated tolytoxin. FR900482 is a recently isolated potent antitumor antibiotic. They both have novel structural features which present challenges to the synthetic chemists. The first total synthesis and structure revision of ($-$)-tantazole B is described herein. A convergent methodology is developed and could be applied to the synthesis of the other members of oxazole/thiazoline family.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) The first and, to date, only total synthesis of $(\pm)$-FR900482 is also described here. The stereocontrolled total synthesis of FR900482 features a facile construction of the 8-membered intermediate through reductive amination, stereospecific hydroxymethyla-tion and efficient oxidation of the amine to the hydroxylamine.