Typescript (photocopy).The synthesis of some of the postulated intermediates in the pathway of vitamin B12 biosynthesis, precorrins-4A, -4B and -5, were initiated. The different ring precursors necessary for the precorrins were prepared as racemic mixtures apart from ring C precursors of precorrin-5 and -4A and -4B, which were obtained optically pure from (+)-camphor and pyrrole respectively. A new method was developed to synthesize a meso-substituted symmetrical dipyrromethane which served as a key intermediate in the synthesis of 20-methyluroporphyrin III and its derivative, 12-decarboxylated-20-methyl-uroporphyrin III. Unlike the 20-H analogs, these uro'gens were found to be unstable. From initial experiments, incubation of 20-methyl-uro'gen III with methylase-1 (M-1) enzyme resulted in the production of a chlorins and isobacteriochlorins as detected by high pressure liquid chromatography coupled with UV, while the action of M-1 on 12- decarboxylated-20-methyl uro'gen III did not show production of any methylated porphyrin. A number of substrate analogs for two enzymes, PBG deaminase and ALA dehydratase, involved in the vitamin B12 biosynthesis were synthesized. Three novel oxa analogs of PBG : the oxa analog, 2-aminomethyl-4-(2-carboxyethyl)-3- carboxymethyl furan, the oxa analog of iso PBG, 2-aminomethyl-3-(2-carboxyethyl)- 4-carboxymethyl furan and its hydroxy derivative, 2-hydroxymethyl-3-(2- carboxyethyl)-4-carboxymethyl furan were prepared. These products have been tested with PBG deaminase and found not to be substrates of the enzyme. In parallel with this study, 5-hydroxylevulinic acid (the hydroxy analog of ALA) was synthesized and found not to be a substrate of ALA dehydratase when tested with the enzyme. Another novel analog of PBG, 2-(hydroxy-1-propene)-4-(2-carboxyethyl)- 3-carboxymethyl pyrrole, was synthesized as the Z isomer. The intermediate, 2- (3-phthalimido-1-propene)-4-(2-methoxycarbonylethyl)-3-methoxycarbonylmethyl pyrrole, was found to be unstable and in the presence of traces of water gave 2 - (hydroxy-1-propene)-4-(2-methoxycarbonylethyl)-3-methoxycarbonylm ethyl pyrrole. Interestingly, the action of PBG deaminase on this PBG analog showed the formation of an ES1 enzyme-substrate complex