Total Synthesis of (+)-18-epi-Latrunculol A

Abstract

An enantioselective total synthesis of the cytotoxic latrunculin congener (+)-18-epi-latrunculol A has been achieved. Key steps in the synthetic route include an acid-mediated enone cyclization / equilibration sequence, a Carreira alkynylation, and a late-stage Mitsunobu macrolactonization to construct the macrolide skeleton.

Marine natural products

“…651 have been achieved, with the latter study determining the absolute conguration 631 of the NP. 652,653 Two separate collections of Pachastrissa nux (Koh Tao, Surat Thani Province, and Chumphon Is. National Park, Thailand) yielded the antimalarial trioxazole macrolide kabiramide L 632.…”

Truncated Latrunculins as Actin Inhibitors Targeting Plasmodium falciparum Motility and Host Cell Invasion

“…The activity was not greatly affected when methyl groups were incorporated at the ortho position of the substituted benzoate analogues (23)(24)(25); this meant that although further Figure S2). A selection of the latrunculin core analogues were then assayed in an inhibition of invasion assay to determine the potency of these analogues toward blocking invasion of T. gondii parasites into host fibroblast cells (Table 2).…”

“…Synthesis of the truncated latrunculin core analogue 3b, could potentially be achieved based on the synthesis of latrunculins by Fürstner et al 23,24 or Smith et al 25 Here we describe the successful synthesis of the latrunculin core analogues based on Smith et al's total synthesis of (+)-18-epi-latrunculol A involving alkene metathesis as the key step and utilizing Hoveyda-Grubbs' II catalyst [26][27][28] (Figure 3). 3-Buten-1-ol was TBS protected 29 to obtain 5 and compound 7 was prepared according to literature in 5 steps.…”

“…3-Buten-1-ol was TBS protected 29 to obtain 5 and compound 7 was prepared according to literature in 5 steps. 25 Compounds 5 and 7 were then subjected to alkene metathesis and then treated with 6 M aqueous HCl to effect 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Michael addition of water to the α,β-unsaturated ketone, TBS deprotection and spontaneous ring closure to obtain 9. The hemiketal 9 was then treated with catalytic camphor sulfonic acid in methanol to obtain the methyl ketal 3b (the latrunculin core), which was esterified using EDCI coupling to generate a focus set of analogues (Figure 4).…”

First synthesis of (S)-(+)-hymenoic acid, a DNA polymerase λ inhibitor isolated from Hymenochaetaceae sp

“…TMS or the residual solvent peak in CDCl 3 (at δ H = 7.26) or CD 3 OD (at δ H = 3.30), was used as the internal standard. 13 C-NMR spectra were recorded at 75 MHz with the Jeol JNM-AL300 spectrometer, the peak for CDCl 3 (at δ C = 77.0) or CD 3 OD (at δ C = 49.0) being used as the internal standard. Optical rotations were taken with a HORIBA SEPA-300 polarimeter.…”