John C. Sih

Synthesis of the four isomers of 5-hydroxy-PGI1

We wish to report here the syntheses of (5S, 6R)-5-hydroxy-, (5R, 6R)-5-hydroxy-, (5R, 6S)-5-hydroxy-, and (5S, 6S)-5-hydroxy-PGI1 and their methyl ester derivatives. Treatment of (5R, 6S)-epoxy- and (5S, 6R)-epoxy-PGF1alpha methyl esters with acid washed silica gel afforded (5R, 6R)-5-hydroxy- and (5S, 6S)-5-hydroxy-PGI1 methyl esters; correspondingly, silica promoted cyclization of (5S, 6S)-epoxy- and (5R, 6R)-epoxy-PGF1alpha methyl esters yielded (5S, 6R)-5-hydroxy- and (5R, 6S)-5-hydroxy-PGI1 methyl esters. Alternatively, the 5-hydroxyl group was introduced into the PGI1 skeleton via reaction of the 5-mercuric halides with sodium borohydride in the presence of oxygen. Stereochemical assignments were based on their mode of synthesis and 1H nmr shift differences.

The synthesis of 2,3-dinorprostacyclin metabolites—a new approach to spirolactone hemiacetals

Abstract The major human urinary metabolites of prostacyclin and 6-keto-PGF 1 α have been synthesized by a direct route, involving three-carbon homologation of bicyclic lactone intermediates and spontaneous spirolactonization of the products. The fact that these 2,3-dinor-6-oxo metabolites exist almost exclusively as spirolactone hemiacetals under acidic conditions (pH 5 and below) may explain the reported difficulties in derivatizing samples of biological origin. Several 19,19,20,20-d 4 metabolites have also been synthesized.

DIFFERENCES IN REACTIVITY AND ENANTIOSELECTIVITY IN LIPASE REACTIONS WITH CARBOXYLIC ESTERS AND ALCOHOLS BEARING THE SAME STEREOGENIC CENTER

Abstract The reaction rate and stereochemical outcome of lipase reactions obtained with carboxylic esters and alcohols, which contain the same stereogenic center, can be modulated by changing the mode of the lipase reaction, i.e. ester hydrolysis versus alcohol acetylation.

Application of immobilized lipase in production of camptosar (CPT-11)

Lipase fromPseudomonas cepaica (Amano, PS-30) was immobilized on celite and used in organic solvent for the selective acylation of a key alcohol intermediate. The compound was transformed in the synthesis to the anticancer drug Camptosar (CPT-11). Catalyst activity was influenced by the water content and method used to dry the catalyst. This resolution has been conducted on production scale with equal weight of recyclable catalyst.

Oxidative ozonolysis of 6-oxo-PGF1α, 11,15-diacetate, methyl acetal, methyl ester

Ozonolysis of 6-oxo-PGF1alpha, 11,15-diacetate, methyl acetal, methyl ester followed by oxidative workup and treatment with diazomethane gave 3-acetoxy-5-hydroxy-2-(methoxycarbonyl) cyclopentane acetic acid, gamma-lactone and dimethyl 3-acetoxy-5[[-(methoxycarbonyl)valeryl]oxy]-1,2-cyclopentane dicarboxylate as two of the major products. The mass spectral properties of the latter compound were identical with those previously published by other investigators.

Synthesis of 2, 3-dinor-PGFα metabolites

Thir report described the preparation of various 2,3-dinor-PGFα prostaglandins. Of particular importance is the synthesis of 2,3-dinor-15(S)-15-methyl PGF2α, the primary metabolite in the enzymatic degradation of 15(S)-15-methyl-PGF2α (1). Introduction of the three carbon β,γ-unsaturated carboxyl side chain was achieved in a one-step Wittig reaction. The 2,3-dinor structural assignments were established by carbon magnetic resonance (crm) spectroscopy.

Synthesis of (19R)-19-hydroxy-PGE and -PGF prostaglandins

Abstract We wish to report here the total synthesis of the naturally occurring (19R)-19-hydroxy-prostaglandins of the PGE and PGF series.

2-(aminomethyl)-2-decarboxyprostaglandin F2α type analogs

Abstract The 2-(aminomethyl)-2-decarboxy analogs of prostaglandin F2α (PGF2α), ( 15S )-15-methyl-PGF2α, 16-phenoxy-ω-tetranor-PGF2α and 16,16-dimethyl-PGF2α were synthesized. The amino analogs closely resemble the parent PGF2α compounds as antifertility agents in the hamster.