Asymmetric Total Synthesis of Leucosceptroid B

Abstract

Scheme 1. Structures of leucosceptroids A-D. Scheme 2. Retrosynthetic analysis of leucosceptroid B. R = protecting group.

A Geranylfarnesyl Diphosphate Synthase Provides the Precursor for Sesterterpenoid (C25) Formation in the Glandular Trichomes of the Mint Species Leucosceptrum canum

“…To identify these unknown peaks, GT exudates were collected by wiping the fresh leaves with an acetone-soaked cotton swab, and the major components were separated by column chromatography followed by semipreparative HPLC purification. Through comparison of their 1 H NMR and 13 C NMR spectra with those of the sesterterpenoids previously isolated from L. canum, three additional peaks with retention times of 28.0, 29.0, and 30.9 min were identified as leucosceptroids I (2) and J (3) (Luo et al, 2013b), and 11-bH-leucosceptroid B (4) (Huang et al, 2013), respectively. Considering that compounds 4 and 5 were major peaks in all organs, the combined amount of these two compounds was quantified by HPLC using purified compounds as external standards.…”

The direct oxidative diene cyclization and related reactions in natural product synthesis

“…This family of sesterterpenoids is believed to be beneficial to the plant as part of a defense mechanism against herbivores. The first total synthesis of leucosceptroid B ( 105b ) was established in 2013 by Huang et al [167] and two other total syntheses of leucosceptroids A ( 105a ) and B ( 105b ) followed two years later [168–169]. The common tricyclic core structure of the natural products had already been synthesized in 2011 by the Horne group [170], using a TPAP-catalyzed type B oxidative cyclization to form the densely substituted THF diol motif following a protocol of our group [25] (Scheme 22).…”

Total Synthesis of Leucosceptroids A and B

“…[5] Two years later, Liu and co-workers achieved the first total synthesis of leucosceptroid B in 2.7 % overall yield from commerically unavailable (S)-5-methyl-5,6-dihydro-2H-pyran-2-one. [6] Recently, Magauer and Hugelshofer accomplished the first total synthesis of norleucosceptroids A and B. [7] Herein, we describe a more efficient and scalable route for assembling leucosceptroid B and the first total synthesis of leucosceptroid A.…”

“…[6] To avoid this problem of isomerization, we planned to obtain a trans-hydrindanol intermediate first and subsequently convert it into 2 at the final step. Consequently, triol 3, which could be assembled by a SmI 2 -mediated 6-exo cyclization of ketone 4, became our next synthetic target .…”

“…[8] Indeed, poor conversion for epimerization of the cis isomer 2 greatly reduced the synthetic efficiency in the leucosceptroid B synthesis developed by Liu and co-workers. [6] To avoid this problem of isomerization, we planned to obtain a trans-hydrindanol intermediate first and . subsequently convert it into 2 at the final step.…”