A C₂-Symmetric Chiral Pool-Based Flexible Strategy: Synthesis of (+)- and (−)-Shikimic Acids, (+)- and (−)-4-epi-Shikimic Acids, and (+)- and (−)-Pinitol

Abstract

Via combination of a novel acid-promoted rearrangement of acetal functionality with the controlled installation of the epoxide unit to create the pivotal epoxide intermediates in enantiomerically pure form, a simple, concise, flexible, and readily scalable enantiodivergent synthesis of (+)- and (-)-shikimic acids and (+)- and (-)-4-epi-shikimic acids has emerged. This simple strategy not only provides an efficient approach to shikimic acids but also can readily be adopted for the synthesis of (+)- and (-)-pinitols. These concise total syntheses exemplify the use of pivotal allylic epoxide 14 and its enantiomer ent-14. A readily available inexpensive C2-symmetric L-tartaric acid (7) served as key precursor. In general, the strategy here provides a neat example of the use of a four-carbon chiron and offers a good account of the synthesis of functionalized cyclohexane targets.

Stereodivergent Syntheses of All Stereoisomers of (−)‐Shikimic Acid: Development of a Chiral Pool for the Diverse Polyhydroxy‐cyclohexenoid (or ‐cyclohexanoid) Bioactive Molecules

“…Only one synthesis of (+)‐4‐ epi ‐ ent ‐SA ent ‐ 3 from L ‐tartaric acid has been reported by Yan et al . in 2014 [24] . Herein we disclose a new synthesis of (+)‐4‐ epi ‐ ent ‐SA ent ‐ 3 from (−)‐SA 1 according to the route depicted in Scheme 2.…”

“…Later, Yan et al . reported a synthesis of (−)‐4‐ epi ‐SA 3 from L ‐tartaric acid in 2014 [24] . Our novel and efficient synthesis of (−)‐4‐ epi ‐SA 3 starting from (−)‐SA 1 was depicted in Scheme 3.…”

Stereodivergent routes in organic synthesis: marine natural products, lactones, other natural products, heterocycles and unnatural compounds

“…Yan and coworkers 74 have described enantiodivergent routes to (+)-and (−)-shikimic acids, (+)-and (−)-4-epi-shikimic acids and (+)-and (−)-pinitols starting from L-tartaric acid. In Scheme 48 the enantiodivergent strategies to both enantiomers of shikimic acid from a common vinyl epoxide has been depicted.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…226) [595], sculponeatin N [596], vitamin D derivatives [597], ryanodol (e.g. [598], shikimic acids and pinitol [599], carbasugars [600], madangamine D ( a later step forms a macrocyclic amine via RCM) [601], the kaurene core [602], various securinega alkaloids [603], a labyssomicin C derivative (e.g. 228 in a moderately diastereoselective RCM using a substrate featuring diastereotopic vinyl groups) [604], the crotogoudin ring system [605], tetrahydrocannabinol derivatives (e.g.…”