Total Synthesis and Stereochemical Revision of Acortatarins A and B

Abstract

A first total synthesis of acortatarins A, B, and an enantiomer of the proposed structure of acortatarin B is described by using readily available d-sugars. This convergent total synthesis revealed the revision of the absolute configuration of acortatarin A and structural revision of acortatarin B. The key steps involved are regioselective epoxide opening with deprotonated 2,5-disubstituted pyrrole and spiroketalization.

Xylapyrrosides A and B, two rare sugar-morpholine spiroketal pyrrole-derived alkaloids from Xylaria nigripes: isolation, complete structure elucidation, and total syntheses

“…6 Due to the intriguing structures, this class of alkaloids attracted considerable interest for organic synthesis soon after their isolation. So far, several groups have accomplished the total syntheses of acortatarins A [8][9][10][11][12] and B. 8,9 Inexplicably, the absolute configurations of the naturally occurring acortatarins were initially assigned by both single-crystal X-ray (MoKα) diffraction analysis and the modified Mosher's method, 5 but they were eventually revised after stereoselective total syntheses.…”

“…So far, several groups have accomplished the total syntheses of acortatarins A [8][9][10][11][12] and B. 8,9 Inexplicably, the absolute configurations of the naturally occurring acortatarins were initially assigned by both single-crystal X-ray (MoKα) diffraction analysis and the modified Mosher's method, 5 but they were eventually revised after stereoselective total syntheses. 8 Meanwhile, acortatarin A was found to be identical with pollenopyrroside B.…”

“…8,9 Inexplicably, the absolute configurations of the naturally occurring acortatarins were initially assigned by both single-crystal X-ray (MoKα) diffraction analysis and the modified Mosher's method, 5 but they were eventually revised after stereoselective total syntheses. 8 Meanwhile, acortatarin A was found to be identical with pollenopyrroside B. 9,10 As a part of our continuing interest in novel bioactive alkaloids from nature, 1,2,13 four sugar-morpholine spiroketal pyrrole-derived alkaloids (1−4, Figure 1) were isolated from the EtOH extract of the dried mycelia of Xylaria nigripes (Koltz.)…”

Synthesis of 5,6- and 6,6-Spirocyclic Compounds

“…Scheme 8 Kulinkovich coupling/ring-opening strategy toward mono(benzannulated) spiroacetals [52] Scheme 9 HWE/chemoselective reduction strategy toward mono(benzannulated) spiroacetals [53] Scheme 10 HWE/deprotection strategy toward mono(benzannulated) spiroacetals [53] A recent example of the use of dehydrative spirocyclization for the synthesis of a heteroannulated spiroacetal natural product is Sudhakar et al's synthesis of the acortatarins 37 and 38 [54] (Scheme 11).…”

“…Scheme 11 Sudhakar et al's synthesis of acortatarins A and B [54] In this case the use of allyl ether-protecting groups allowed their removal under pH neutral conditions. Thus, treatment of 44 with catalytic Pd(0) in the presence of a polymethylhydrosiloxane-zinc chloride complex (PMHS-ZnCl 2 ) afforded the spiroacetal core of paecilospirone in good yield, as a 3.5:1 mixture of anomers.…”