Organocatalytic asymmetric syntheses of inthomycins A, B and C

Abstract

The total syntheses of (+)-inthomycin A, (+)-inthomycin B and (-)-inthomycin C, the oxazole-triene antibiotics isolated from Streptomyces sp., have been accomplished via the highly enantio- and stereoselective construction of the C1-C7 (iododienyl)aldol units by taking advantage of a Cinchona alkaloid-catalyzed asymmetric β-lactone synthesis and their isomerisation-free Stille coupling with (E)-5-(3-(tributylstannyl)allyl)oxazole.

Short, Tin‐Free Synthesis of All Three Inthomycins

“…[25] After extensive experimentation we found that the use of palladium(II)a cetate and triphenylphosphine in the presenceo f 1 m aqueouss odium bicarbonate allowed the union of the dienylboronic ester 15 with the (Z)-alkenyl iodide (Z)-17 to proceed with complete stereochemical fidelity to give the correspondingc oupled product 19 in 64 %y ield. Double deprotection of the triene 19 with HF in acetonitrile [9] gave the alcohol 20 which wasc onverted into inthomycin B 2 via aminolysis of the corresponding pentaflurorophenyl ester 21.O ur synthetic For the synthesis of inthomycin C 3,t he Suzukic oupling between the (Z,Z)-dienyl boronate 15 and the (E)-alkenyl iodide (E)-17 required furthero ptimization. Ultimately,w ef ound that the concentration of aqueous base proved crucial with the use of 0.25 m sodium bicarbonate giving the coupled product 22 in 65 %y ield.…”

Total Synthesis of Biologically Active Natural Products Based on Highly Selective Synthetic Methodologies

“…In addition to the total syntheses presented in this review, we also achieved the syntheses of a variety of biologically active natural products with structural challenges such as febrifugine, 114) viridiofungin A, 115) trachyspic acid, 116) cinatrin C 1 , 117) β-erythroidine, 118) NW-G01, 119) inthomycins A-C, 120) englerin A, 121) ophiodilactones A and B, 122) and marinomycin A. 123) The strategies and methodologies we have developed are of great potential value in synthetic organic chemistry as well as pharmaceutical research.…”

The oxazolomycin family: a review of current knowledge

“…The most common framework is the oxazole-triene-amide 18 also known as inthomycin derivative. 19 Inthomycin A (16; Fig. 2) with (4Z,6Z,8E)-congurated triene is present in the structures of oxazolomycin A, oxazolomycin A2, neooxazolomycin, 16-methyloxazolomycin, curromycin A, curromycin B, KSM-2690 B and in the both segments of bisoxazolomycin.…”