The Absolute Configuration for Inthomycin C: Revision of Previously Published Work with a Reinstatement of the (3R)-Configuration for (−)-Inthomycin C

Abstract

Stereochemical evidence is presented to demonstrate that (-)-inthomycin C has (3R)- and not (3S)-stereochemistry. Careful reappraisal of the previously published work2-5 now indicates that the Hatakeyama, Hale, Ryu, and Taylor teams all have synthesized (-)-(3R)-inthomycin C. The newly measured [α]D of pure (-)-(3R)-inthomycin C (98% ee) is -7.9 (c 0.33, CHCl3) and not -41.5 (c 0.1, CHCl3) as was previously reported in 2012.

Asymmetric Total Synthesis of (−)-(3R)-Inthomycin C

“…Analytical data are in accordance with those previously reported for this compound. 13,[16][17][18][19] Alcohol Analytical data are in accordance with those previously reported for this compound. 13,16,17 S18…”

Short, Tin‐Free Synthesis of All Three Inthomycins

“…Importantly, the absolute configuration of inthomycin C 1 has been the subject of much confusion and debate in the literature. However, recently these ambiguities have been laid to rest by Hale and Hatakeyama with the absolute configuration of inthomycin C 1 being firmly established as ( R ) confirming the original assignment by Henkel and Zeek . We had assigned the absolute configuration of the alkenyl iodides ( Z )‐ 5 and ( E )‐ 5 as ( S ) using Kakisawa's extension of Mosher's method which translates into the absolute configuration of all of the inthomycins being ( R ), and our optical rotation for 3 was in agreement with the recently remeasured values …”

Enantiospecific Formal Synthesis of Inthomycin C

“…were shown to have very interesting biological activities like specific inhibition of cellular biosynthesis, selective in vitro antimicrobial activity and reduction of prostate cancer cell growth . Although it looks like a simple structure, inthomycin C 1 has posed several challenges to the synthetic community and has also resulted in a few inconsistencies . A recent resynthesis of 1 through painstaking efforts by Hale & Hatakeyama groups jointly resolved the discrepancy associated with this target.…”

“…A recent resynthesis of 1 through painstaking efforts by Hale & Hatakeyama groups jointly resolved the discrepancy associated with this target. The details of evolution of events can be found in the same publication ( Organic Letters , 2014) . Here, we have summarized the highlights of events with respect to inthomycin C in Table starting from its isolation in the year 1991 to recent efforts.…”

“…Here, we have summarized the highlights of events with respect to inthomycin C in Table starting from its isolation in the year 1991 to recent efforts. Although several synthesis are documented and controversies are resolved, all syntheses relied on enantioselective methods using chiral reagents including very recent syntheses . Because of interesting biological activity, structural features and occurrence of several related molecules in the nature, we decided to develop a route to synthesize target compound 1 in an enantiospecific manner.…”