Synthesis of Prostaglandin and Phytoprostane B₁ Via Regioselective Intermolecular Pauson−Khand Reactions

Abstract

A new approach to the synthesis of prostaglandin and phytoprostanes B(1) is described. The key step is an intermolecular Pauson-Khand reaction between a silyl-protected propargyl acetylene and ethylene. This reaction, promoted by NMO in the presence of 4 A molecular sieves, afforded the 3-tert-butyldimethylsilyloxymethyl-2-substituted-cyclopent-2-en-1-ones (III) in good yield and with complete regioselectivity. Deprotection of the silyl ether, followed by Swern oxidation, gave 3-formyl-2-substituted-cyclopent-2-en-1-ones (II). Julia olefination of the aldehydes II with the suitable chiral sulfone enabled preparation of PPB(1) type I and PGB(1).

New Bioactive Oxylipins Formed by Non‐Enzymatic Free‐Radical‐Catalyzed Pathways: the Phytoprostanes

“…)-trans,trans-dPPJ 1 type II 38 in good yield (Scheme 6). In 2009, Riera and coworkers developed a new approach using an intermolecular Pauson-Khand reaction of internal alkynes (Scheme 7) for the synthesis of PGB 2 and PPB1 [44].…”

“…THF, 0°C quant. Scheme 7 Synthesis of PPB 1 type I according to Riera et al[44] 16-epi-16-E 1 -PhytoP 57 1. n-BuLi, CuCN, MeLi Et 2 O, −78° C to −40° C Scheme 10 Synthesis of PPE 1 according to Spur et al[50] …”

A Divergent Enantioselective Synthesis of 9‐J1‐Phytoprostane and 9‐A1‐Phytoprostane Methyl Ester

“…Under these conditions, the elusive 9‐A 1 ‐PhytoP ( 2 ) was obtained as its methyl ester (i.e., 21 ) in 65 % isolated yield, [ α ] D 20 = 67.5 ( c = 0.12, CH 2 Cl 2 ). The extreme instability of the 9‐A 1 ‐phytoprostane structure is reflected in both the yield of the crucial Dess–Martin oxidation (31 %) en route to 20 , and the extensive decomposition of 9‐A 1 ‐PhytoP methyl ester 21 that was observed during an attempted hydrolysis under extremely mild CAL‐B mediated conditions 15…”

Metallacycle-mediated cross-coupling in natural product synthesis

“…In selecting examples that highlight cross-coupling-based Pauson-Khand reactions in natural product synthesis, attention has been paid to highlight those that use coupling partners more complex than ethylene. 137–139 …”