Hennoxazole

More recent examples have employed a milder reagent system, triphenyl-phosphine and dibromotetrachloroethane to generate a bromo-oxazoline, which is subsequently dehydrohalogenated. Wipf and Lim utilized their method to transform intermediate 11 into the 2,4-disubstituted system of (+)-Hennoxazole k Subsequently, Morwick and coworkers reported a generalized approach to 2,4-disubstituted oxazoles from amino acids using a similar reagent combination, triphenylphosphine and hexachloroethane. ... 

New methods for the synthesis of 2,4-disubstitued oxazoles are summarized in a recent review. 2-Alkyl-1,3-oxazoles bearing alkyl, aryl, or acyl substitution at C4 are common substructures in natural products. Examples include macrolides such as rhizoxin (4), hennoxazole A (5), and phorboxazole A (6), ° as well as many cyclic peptides that incorporate an oxazole subunit presumably derived from serine. ... 

Wipf, P. Lim, S. (1996) Total synthesis and structural studies of the antiviral natural product hennoxazole A. Chimia, 50, 157-67. 

SCHEME 62. Synthesis of hennoxazole A via Pd-catalyzed alkenyl-allyl coupling... 

The transmetallation process was extended to the preparation of vinylboranes709,710, and the superior reactivity of organotins over organosilicons was elegantly demonstrated by Williams and coworkers for the preparation of the optically active allylborane 24 from the corresponding allylic stannane in the total synthesis of (—)-Hennoxazole A711 (equation 54). 

In the synthesis of (—)-hennoxazole (37), Wipf and Lim used a CBS reagent to prepare the chiral allylic alcohol 3918 (Scheme 4.3n). The enantioselective reduction of the enone 38 using a catalytic amount of the oxazaborolidine 28b... 

S )-epichlorohydrin, have been used in the synthesis of leucascandrolide A289 and (—)-hennoxazole A290, respectively. 

During a synthesis of Hennoxazole, Wipf and Lim97 found that Lithium hydroxide at 90 3 C offered a convenient method for removing a TBS ether in the presence of a TIPS ether [Scheme 4.59], This is a rare example of the use of basic hydrolysis in selective alkyl silyl ether deprotection. 

The total synthesis of the antiviral marine natural product (-)-hennoxazole A was accomplished by F. Yokokawa and co-workers." The mild reduction of a secondary alkyl azide at C9 was carried out using triphenylphosphine in a THF/water mixture at slightly elevated temperature. The corresponding primary amine was obtained in good yield and was subsequently acylated and converted to one of the oxazole rings of the natural product. 

The antiviral marine natural product, (-)-hennoxazole A, was synthesized in the laboratory of F. Yokokawa." The highly functionalized tetrahydropyranyl ring moiety was prepared by the sequence of a Mukaiyama aldol reaction, cheiation-controiied 1,3-syn reduction, Wacker oxidation, and an acid catalyzed intramolecular ketalization. The terminal olefin functionality was oxidized by the modified Wacker oxidation, which utilized Cu(OAc)2 as a co-oxidant. Interestingly, a similar terminal alkene substrate, which had an oxazole moiety, failed to undergo oxidation to the corresponding methyl ketone under a variety of conditions. 

Yokokawa, F., Asano, T., Shioih, T. Total Synthesis of the Antiviral Marine Natural Product (-)-Hennoxazole A. Org. Lett. 2000, 2, 4169-4172. 

Directly linked bisoxazole core as a unique feature of hennoxazole A s structure is only found in the polycyclic marine alkaloids diazonamides A-B and cyanobacterium derived muscoride A and hennoxazole A. The marine natural product hennoxazole A was synthesized by a convergent synthesis [1]. 

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