Hydroxylation of prostanoids by fungi. Synthesis of (−)-15-deoxy-19-(R)-hydroxy-PGE₁ and (−)-15-deoxy-18-(S)-hydroxy-PGE₁

Abstract

A series of racemic substituted cyclopentanones, with alkyl groups corresponding to the upper prostanoid side chain and (or) the lower prostanoid side chain without the C-15 alcohol, has been synthesized. Using a steroid template for the prostanoid molecule as a basis for selection, fungi capable of hydroxylating steroids have been used to biotransform the prostanoid substrates. The predominant products were hydroxylated at the prostanoid C-18 and C-19 positions. The hydroxylations were enantioselective, with excesses in the range 10-60%, and in most cases the predominant configuration corresponded to that of the natural prostanoids. The stereochemistry of the C-19 hydroxyl group was found to be R by degradation of products to methyl 6-acetoxyheptanoate and comparison of that material with a resolved sample, obtained via crystallization of the brucine salt of ethyl 6-phthaloxyheptanoate. Hydroxylation at C-18 gave the S configuration of alcohol. Hydroxylation at prostanoid C-15 was observed, but in all cases this was accompanied by other reactions. Hydroxylation of Rhizopus arrhizus has been used in a preparation of ( Chem. 68, 282 (1990). On a synthttist une sCrie de cyclopentanones substitukes ractmiques portant des groupements alkyles correspondant a la chaine laterale prostano'ide supCrieure et (ou) a la chaine lathale prostanoide infkrieure ne portant pas la fonction alcool en C-15. Utilisant comme base de sClection un gabarit stCroi'dal pour representer la molCcule prostanoi'de, on a fait appel a un champignon capable d'hydroxyler les stkroides pour effectuer la biotransformation des substrats prostanoldes. Les produits principaux sont les prostano'ides hydroxylCs en positions C-18 et C-19. Les hydroxylations sont CnantiosClectives, avec des excks de l'ordre de 10-60%, et, dans la plupart des cas, la configuration prCdominante correspond a celle des prostanoYdes naturels. En se basant sur une dkgradation des produits en 6-acCtoxyheptanoate de mCthyle et sur une comparaison de ce produit avec un Cchantillon rtsolu, obtenu par cristallisation du sel de brucine du 6-phtaloxyheptanoate d'ithyle, on a dCmontrC que la stCrCochimie du groupement hydroxyle en C-19 est R. L'hydroxylation en C-18 foumit un alcool de configuration S. On a observt une hydroxylation en C-15 du prostano'ide; toutefois, cette reaction est toujours accompagnee par d'autres reactions. On a fait appel une hydroxylation par le Rhizopus arrhizus pour la prkparation des (-)-15-dCsoxy-19-(R)-hydroxy-PGWI et (-)-15-dCsoxy-18-(S)-hydroxy-PGW,.

4‐Heterosubstituted Cyclopentenone Antiviral Compounds: Synthesis, Mechanism, and Antiviral Evaluation

“…Racemic 4‐oxocyclopent‐2‐en‐1‐yl acetate [(±)‐ 10 ] was prepared by acetylation12 of 4‐hydroxy‐2‐cyclopentenone [(±)‐ 9 ]10,13 in the presence of acetic anhydride and pyridine in THF as solvent.…”

Biotransformation Reactions by Rhizopus spp.

“…The prostanoid ester 150 with R. oryzae, for example, resulted in ester hydrolysis to give 151 (18%) (Scheme 16) [48]. The bioconversion of prostanoid 152 gave hydroxylation at C-19 yielding 153 (8%) with reduction of the carbonyl compound 154 (11%), while the microbial transformation of prostanoid ester 155 yielded the hydrolyzed metabolites 156-158 with concomitant hydroxylation at C-18 (8%) and C-19 (10%) [49].…”

Efficient Piancatelli rearrangement on a large scale using the Zippertex technology under subcritical water conditions

“…36,37 On a large scale, following the procedure reported by Nanni et al, furfuryl alcohol (FA) can be converted into the desired 4-hydroxy-2-cyclopentenone (HCP). This transformation requires a deionized and degassed water solution of phosphate buffer using dihydrogen orthophosphate and phosphoric acid (pH 4.1) 38 and has been implemented for the synthesis of prostaglandin derivatives [39][40][41] and 2-cyclopenten-1,4-diol derivatives [42][43][44][45] to prepare building blocks for the synthesis of more complex compounds [46][47][48][49][50] and for resolution studies of racemic HCP. [51][52][53] However, these thermal conditions required a long reaction period (2 days) and high dilution and delivered the desired HCP in modest yields (30-40%) due to the formation of numerous side-products and a dark brown polymeric material.…”