Enantioselective synthesis of the 13-membered macrodiolide bartanol

Abstract

The enantioselective synthesis of the unusual 13-membered ring macrodiolide bartanol7 from poly [(R)hydroxybutyrate] is described confirming the 6R,llR,13R configuration of the natural product. The use of a novel ylide 29 with a MEM-ester protecting group is developed to enable a mild, one-pot cleavage of both the acid and alcohol protecting groups in 30 prior to macrocyclisation to the bartanol framework. The outcome of a Wittig chain extension reaction on a mixture of lactols 19 and 22 using this ylide was found to be dependent on the solvent.

First Total Synthesis of Grahamimycin A

“…The combined EtOAc phases were dried and concentrated to give an oil, which was purified by chromatography (hexane/EtOAc) to afford acid 6 (5.87 g, 81%). The 1 H NMR spectrum of 6 was in good agreement with that reported …”

“…The residual oil was purified by chromatography (hexane/EtOAc) to afford ester 21 (9.16 g, 76%). The 1 H NMR spectrum of 21 was in good agreement with that reported …”

“…Another fragment 6 proposed in Scheme was prepared from aldehyde 11 , the intermediate used in Scheme , according to a modification of Simpson's procedure. Thus, the Wittig reaction of 11 with (EtO) 2 P(O)CH 2 CO 2 Et under the conditions developed by Masamune (DBU, LiCl, MeCN) afforded ester 21 , which was not contaminated with the cis isomer (geometric isomer purity >95% by 1 H NMR spectroscopy), and hydrolysis then gave 6 in 62% yield (Scheme ).…”

Macrolactonizations in the Total Synthesis of Natural Products

“…Several other proton sources have been used in Boden−Keck type macrolactonizations, such as DMAP−TFA, ,− TsOH, and camphorsulfonic acid (CSA). − …”

Update 1 of: Macrolactonizations in the Total Synthesis of Natural Products

“…XXXX, XXX, XXX−XXXO also been used in the trimerization of a seco-acid to obtain the triolide arthrobacilin 607. Several other proton sources have been used in Boden−Keck type macrolactonizations, such as DMAP−TFA, 53,608−614 TsOH,615,616 and camphorsulfonic acid (CSA). 617−619…”