Synthesis of diospongin A, ent-diospongin A and C-5 epimer of diospongin B from tri-O-acetyl-D-glucal

Abstract

We describe a new synthesis of diospogin A, its enantiomer ent-diospongin A and C-5 epimer of diospongin B from commercially available tri-O-acetyl-D-glucal, based on a copper catalyzed Michael addition of phenyllitium to the corresponding ,-unsaturated ketone. The stereochemical course of the Michael addition was unambiguously established by X-ray crystallographic analysis.

Advances in the Synthesis of Natural Products and Medicinally Relevant Molecules from Glycals

“…3,4,6-tri-O-acetyl-D-glucal (17) has been used as a cheap starting material for the synthesis of biologically active Diospongin A (38) and ent-diospongin (34) natural products by Fall and co-workers (Scheme 4). [17] Initially glucal17 is converted to α, β-unsaturated ketone 29 via three steps which subsequently undergo the copper-catalyzed Michael addition of phenyl lithium to give a separable mixture of diastereomeric ketones 30 and 31 in a 1 : 1 : 2 ratio. Stereoselective reduction of compounds 30 and 31 followed by the subsequent side chain elaboration led to desired compounds ent-diospongin A (34) and diospongin A (38) respectively in good yields.…”

“…Pieter et al reported [31] , the synthesis of the papulacandin D derivatives which is differing by acid side chain group from Papulacandin D. Initially they synthesized anomeric activated glucal derivative (90) from tri-O-acetyl D-glucal (17). The aglycon moiety (81) in Papulacandin D was synthesized by using 3, and 5-hydroxy benzoic acid.…”

“…[15] Yu and co-workers reported the convergent synthesis of 16 in 19 % overall yield (Scheme 3). [16] The group constructed a C1-C7 fragment of 16 from commercially available 3,4,6-tri-O-acetyl-D-glucal (17). The heating of glu-cal17 in water gives hemiacetal, which upon subsequent hydrogenation yielded saturated hemiketal 18 as a diastereomeric mixture.…”

Synthetic Approaches to Diospongins: A Two Decade Journey

“…The synthesis of (–)-diospogin A ( 1 ) and ent -diospongin A ( 3 ) was demonstrated by Fall et al from tri - O -acetyl- d -glucal, by using copper-catalysed Michael addition of phenyllitium. 27 Initially, compound 92 was synthesized from 91 in two steps. Next, 92 was subjected to PDC-mediated oxidation to form α,β-unsaturated ketone 93 followed by copper-catalysed Michael addition of PhLi, to give diastereomeric ketones 94a and 94b .…”

Untitled

“…The synthesis of (-)-diospogin A (1) and ent-diospongin A (3) was demonstrated by Fall et al from tri-O-acetyl-Dglucal, by using copper-catalysed Michael addition of phenyllitium. 27 Initially, compound 92 was synthesized from 91 in two steps. Next, 92 was subjected to PDC-mediated oxidation to form ,-unsaturated ketone 93 followed by copper-catalysed Michael addition of PhLi, to give diastereomeric ketones 94a and 94b.…”