ABSTRACT
Starting from ergosterol two novel 9,11-secosterols with modified side chains (1a) and (1c) were synthesized via eight main transformations.
Subject(s)
Cnidaria/chemistry , Secosteroids/isolation & purification , Animals , Candida/enzymology , Cell Cycle/drug effects , Chromatography, Thin Layer , Enzymes, Immobilized , Fungal Proteins , Lipase/metabolism , Mass Spectrometry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Secosteroids/chemical synthesis , Secosteroids/chemistry , Spectrophotometry, Infrared , Spectrophotometry, UltravioletABSTRACT
Natural prostaglandins (PG) F2alpha and E1 as well as (+)-cloprostenol were regioselectively 11-acylated using Novozym 435 as a catalyst and vinyl acetate as an acyl donor. Unlike the above compounds the 15-OH group of PGE2 was also acylated with a significant velocity under the same conditions. The enantiospecificity of the lipase-catalysed 11-acetylation of cloprostenol was established by separate treatment of(+)- and (-)-cloprostenols.
Subject(s)
Lipase/metabolism , Prostaglandins/metabolism , Acylation , Magnetic Resonance SpectroscopyABSTRACT
Bicyclo[3.2.0]heptane analogues of prostacyclin were synthesized starting from 2,3-epoxy-bicyclo[3.2.0]heptane-6-one ethylene ketale by means of alkynydlithium-BF3-reagents and Wittig reaction. The regioselectivity of the oxirane ring opening reaction is 3:2 and stereoselectivity of Wittig olefinization is 1:1. The synthesised compounds were identified by 13C NMR spectra. The antiaggregative activity of the prostacyclin analogues on rabbit blood platelets was 10(-3)-10(-4) of the activity of PGE1, the isomers with (E)-double bond in alpha-chain being by an order more active that the (Z)-isomers. Elongation of the alpha- and omega-side chain by one carbon atom gives 2-4 fold increase of the activity. Bicyclo[3.2.0]heptane analogues of prostacyclin represent-simple and readily obtainable models for elucidation of structure-activity relationship among prostacyclin analogues.
