Synthesis of side chain truncated apicularen A

Abstract

The potent cytostatic agent apicularen A belongs to a growing class of macrocyclic salicylates with unique biological properties. Herein, we present a short enantioselective synthesis of side chain truncated apicularen A.

A Carbohydrate Approach for the First Total Synthesis of Cochliomycin C: Stereoselective Total Synthesis of Paecilomycin E, Paecilomycin F and 6′‐epi‐Cochliomycin C

“…The aromatic ester 11 was synthesized following the known protocol starting from 2,4,6-trihydroxybenzoic acid (THBA) (12) (Scheme 4). Compound 9 was subjected to one pot acetonide deprotection followed by esterification with alcohol 20 employing NaH at 0°C under De Brabander's conditions [25] to furnish the desired ester 24 in 76 % yield. Regioselective methylation under Mitsunobu conditions [23] furnished methyl ether 22.…”

Total Synthesis and Biological Evaluation of (−)Apicularen A and Analogues Thereof

“…The next step, aiming at formation of the macrocycle, parallels the NaH procedure utilized by DeBrabander and Bhattacharjee [17] in their synthesis of apicularen A. However, in this instance the use of excess NaH (7.0 equiv) in THF at ambient temperature, followed by addition of 5.0 equivalents of water (after the macrocycle was formed) resulted in complete deprotection, furnishing the dihydroxylactone 16 in 75 % yield.…”

“…A concise total synthesis of apicularen A (1) and its D 17,18 (Z) isomer (2) has been devised and executed in 16 linear steps. This strategy was adopted for the construction of a series of analogues of the natural substance, biological evaluation of which established a set of interesting structure activity relationships (SAR).…”

5.10 Hetero-Diels–Alder Reactions

“…[16][17][18] The chiral salen-chromium(III) complex 7 (X¼ BF 4 ) catalyzes the hetero-Diels-Alder reaction of 1 with various aldehydes to give the corresponding cyclohexenones with high enantioselectivity (equation 1, Table 1). [16][17][18][19][20][21][22] The addition of oven-dried powdered molecular sieves (MSs) 4 Å to the reactions increases the yield and enantioselectivity. The present reaction is proposed to proceed via a concerted [4 þ 2] mechanism.…”