Asymmetric Total Synthesis of (+)-Inthomycin C via O-Directed Free Radical Alkyne Hydrostannation with Ph₃SnH and Catalytic Et₃B: Reinstatement of the Zeeck–Taylor (3R)-Structure for (+)-Inthomycin C

Abstract

A new pathway to (+)-inthomycin C is reported that exploits an O-directed free radical hydrostannation reaction on (-)-12 and a Stille cross-coupling as key steps. Significantly, the latter process was effected on 19 where a gauche-pentane repulsive interaction could interfere. Our stereochemical studies on the alkynol (-)-12 and the enyne (+)-7 confirm that Ryu and Hatakeyama's (3S)-stereochemical revision of (+)-inthomycin C is invalid and that Zeeck and Taylor's original (3R)-stereostructure for (+)-inthomycin C is correct.

Enantiospecific Formal Synthesis of Inthomycin C

“…Detachment of benzyl group under the specific conditions resulted in the Hatakeyama's enynol (‐)‐2 in 69 % yield (Scheme ). The spectroscopic data ( 1 H, 13 C NMR) of the present compound (‐)‐2 was compared with that of published data from both Hatakeyama and Hale groups and found to be perfectly matching. The [ α ] D value for our sample was recorded as −15.3, which was compared with the independent measurements of Hatakeyama and Hale groups.…”

“…Inthomycin C, a prominent member of inthomycin family of natural products has attracted the attention of many research groups and resulted in several syntheses of the target molecule in recent times . Inthomycins, originally isolated by Zeeck et al .…”

“…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.…”

Asymmetric Total Synthesis of (+)‐Neooxazolomycin Using a Chirality‐Transfer Strategy

“…However, the Z , Z ‐1‐bromodiene 35 was selectively obtained in two steps using Uenishi's protocol, which involves a Corey–Fuchs dibromoolefination and Pd‐catalyzed hydrogenolysis. The Stille coupling of 35 with the known vinyl stannane 36 successfully provided the oxazole triene 37 without significant isomerization of any of the double bonds . The TBS protecting group was removed, and the resulting alcohol was oxidized to the acid by a Swern oxidation followed by a Pinnick oxidation to provide 38 .…”

Synthesis and Biological Evaluation of Amide Derivatives of Thiazoles as Anticancer Agents

“…These have been the focus of great interest due to their significant biological properties such as (6, oxazole) anti-HIV agents 2 , anti-tuberculotic agents 3 , antifungal agents 4 , insecticidal 5 , herbicidal 6 , anti-cancer 7 , inhibitors of receptor tyrosine kinases (RTK) 8 , and A2A adenosine receptor antagonists 9 . Some of the oxazole nucleus contains compounds like Inthomycin C (1) (antineoplastic) 10 , Oxaprozin (2) (antiinflammatory) 11 , Pemoline (3) (nervous system stimulant) 12 . (Figure 1) In addition, 1,3-thiazole are sulfur and nitrogen contain heterocyclic molecules have recently attracted great attention due to their prominent biological activity [13][14][15][16] .…”