Asymmetric Synthesis of Calyculin C. 2. Synthesis of the C₂₆−C₃₇ Fragment and Model Wittig Couplings

Abstract

We report our synthesis of the C(26)-C(37) fragment of serine/threonine protein phosphatase PP1 and PP2A inhibitor calyculin C (1). Outlined in this paper are synthetic approaches to the two components based on disconnection at the C(33)-N(3) amide bond. We report the successful synthesis of the C(33)-C(37) aza-sugar derived from D-lyxose which was coupled onto a C(26)-C(32) aminooxazole originating from L-pyroglutamic acid. Elaboration of the resulting amide to a fully deprotected C(26)-C(37) fragment of calyculin C completed our synthesis. This provided an appropriate phosphonium salt for use in a Wittig olefination for joining both halves of the natural product.

Application of the Nucleotidylyltransferase Ep toward the Chemoenzymatic Synthesis of dTDP‐Desosamine Analogues

“…Standard transformations led to intermediate 19 from which the syntheses of 9, 10 , and 11 diverged. The amino‐ and acetamido‐substituted 9 and 10 followed previously reported strategies from 19 and 21 , respectively 8b, 12. The reduction of 19 and subsequent exhaustive reductive methylation12 led to the dimethyl‐substituted precursor 20 .…”

“…The amino‐ and acetamido‐substituted 9 and 10 followed previously reported strategies from 19 and 21 , respectively 8b, 12. The reduction of 19 and subsequent exhaustive reductive methylation12 led to the dimethyl‐substituted precursor 20 . Substrate 12 was derived from commercially available 22 following similar activation and phosphorylation strategies,8 while substrate 13 derived from the 4,6‐dideoxy glucoside 26 ,13a generated by C4/C‐6 activation and reductive deoxygenation in a fashion similar to a previously described strategies 8a.…”

A Short and Efficient Synthesis of (2S,3S,4S)-tert-Butyl 3,4-Dihydroxy-2-(methoxymethyl)-5-oxopyrrolidine-1-carboxylate

“…The 1 H NMR spectra of 13 was in accordance with data reported in the literature. 11 In conclusion, we were able to synthesize a benzyl-protected C33-C37 fragment of calyculin C in an overall yield of about 7% (over six steps) starting from Z-enoate 2.…”

Calyculins and Related Marine Natural Products as Serine- Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C

“…It can be also noticed that the left half of the fragment resembles serine. This was exploited by the Shioiri, Barrett, and Koskinen groups (Scheme 39) [20,38,65,66]. …”