New synthesis of syn-stereodiad building block for polyketides. Formal synthesis of arenamides A and C

Abstract

An efficient procedure has been developed for the transformation of (7S)-7-(3-bromoprop-1-en-2yl)-5,5-dimethyl-4,6-dioxaspiro[2.5]octane [available from diethyl (S)-malate] into methyl 2-[(4S)-2,2-dimethyl-5-methylidene-1,3-dioxan-4-yl]acetate, and conditions for diastereoselective reduction of the double C=C bond in the latter have been optimized. The reduction product has been converted into (3S,4S)-3-[tertbutyl(dimethyl)siloxy]-4-methyldecanoic acid which is a building block for the synthesis of arenamides A and C, natural compounds possessing pronounced antitumor activity and efficiently inhibiting nitrogen(II) oxide and prostaglandin E 2 (PGE 2 ). * Stereodiad (propionate) block is a three-carbon fragment with vicinal hydroxy and methyl substituents in polyketide molecules.

Selective Carbon–Carbon Bond Cleavage of Cyclopropanols

“…382 There has been a number of total syntheses that have used the oxidative cleavage strategy to form synthetic intermediates (Scheme 187). In this general strategy, treatment of a cyclopropyl alcohol (892) with PhI(OAc) 2 in the presence of either an alcoholic solvent or water will generate the relevant carboxylic acid derivative (893) (Scheme 187a), with ethylene 390 The formations of carboxylic acid 897, an intermediate for the synthesis of epothilone D, 391,392 and carboxylic acid 898, an intermediate for the synthesis of capsaicin, have been reported by Kulinkovich and coworkers. 393 Other applications of this reaction include an intermediate for the synthesis of the C13−C21 fragment of epithilones reported by Kulinkovich and co-workers, 394 and an intermediate for the synthesis of Unit A of the cryptophycins reported by Shklyaruck.…”

“…In this general strategy, treatment of a cyclopropyl alcohol ( 892 ) with PhI­(OAc) 2 in the presence of either an alcoholic solvent or water will generate the relevant carboxylic acid derivative ( 893 ) (Scheme a), with ethylene lost as the side product. Some select examples of this strategy (Scheme b) include the synthesis of the following esters: 894 , an intermediate for the synthesis of (+)-disparlure reported by Kulinkovich and co-workers; 895 , an intermediate for the synthesis of insect pheromones reported by Kananovich and co-workers; and 896 , an intermediate in the formal synthesis of arenamides A and C reported by Shklyaruck . The formations of carboxylic acid 897 , an intermediate for the synthesis of epothilone D, , and carboxylic acid 898 , an intermediate for the synthesis of capsaicin, have been reported by Kulinkovich and co-workers .…”

Generation of Mixed Anhydrides via Oxidative Fragmentation of Tertiary Cyclopropanols with Phenyliodine(III) Dicarboxylates

“…For example, Kirihara and co-workers utilized oxidative fragmentation as the key step in the short synthesis of an alkaloid (−)-pinidine [ 28 , 29 ], while our group reported synthesis of natural macrolactone (+)-recifeiolide via the ring opening-macrolactonization cascade in an aprotic solvent [ 30 ]. On the other hand, cyclopropanol moiety can be considered as a convenient “protecting group” for carboxylate functionality, readily installed by Kulinkovich reaction with ethylmagnesium bromide [ 31 , 32 , 33 , 34 , 35 , 36 ]. The “deprotection” is performed by oxidative cleavage with PIDA and produces ethylene gas as the side product.…”