Access to Skipped Polyene Macrolides through Ring‐Closing Metathesis: Total Synthesis of the RNA Polymerase Inhibitor Ripostatin B

Abstract

Rip-Roaring! A convergent total synthesis of antibiotic ripostatin B was developed. A key step in the synthesis is a metathesis reaction allowing for a ring closure to the labile doubly skipped triene macrolide.

One-Pot Oxidation/Isomerization of Z-Allylic Alcohols with Oxygen as Stoichiometric Oxidant

“…The oxidation of the allylic alcohol 13 is one step in our total synthesis of ripostatin B. 32 The desired aldehyde 14 could be obtained cleanly in 89% yield (entry 8).…”

A Comparative Synthetic Strategy Perspective on α‐Amino Acid‐ and Non‐Amino Acid‐Derived Synthons towards Total Syntheses of Selected Natural Macrolides

“…Mainly,three independent groups have completed the total synthesis of Ripostatin B( 5)i np arallel. [23][24][25] Synthetic approaches using non-AA routes Christmann'sa pproach:C hristmann and co-workersi n2 012 describedt he total synthesiso fR ipostatin B( 5)i n1 4s teps with 4% overall yield (Scheme 2). [23] Geranyl acetate was used as the precursor for two building blocks, 35 and 40,w hich were coupled in one pot by linchpin coupling and later the ring formation was achieved by ring-closing metathesis.…”

Organocatalysis in Total Synthesis

“…Among other examples, α-oxidation is the most frequent one: 7,8-O-isopropylidene iriomoteolide-3a [15], (+)-neosymbioimine [16], (+)-and ()-disparlure [17], ()-(5R,6S)-6-acetoxy-5-hexadecanolide [18], and Hagen's gland lactones [19]; followed by α-amination: chloptosin [20], (S)-AIDA [21], and Licopodium alkaloids [22]. Sometimes α-heterofuntionalization of carbonyl compounds is necessary to form a temporal reactive intermediate, as is the case of α-selenylation: (+)-symbioramide [23], and α-chlorination: ripostatin B [24]. Moreover, organocatalytic Michael addition is other main C-C bond-forming strategy widely used in natural product synthesis.…”