Efforts toward the total synthesis of 7-deoxyzaragozic acic A and galtamycinone
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Studies toward the total synthesis of 7-deoxyzaragozic acid A (2.56) were intended to build upon the completion of the synthesis of 6,7-dideoxysqualestatin H5 (2.47) that featured the stereoselective intramolecular vinylogous aldol reaction of the furoic ester 2.23a to give 2.26 or its trimethylsilyl ether derivative 2.30, which possess the requisite absolute stereochemistry at C(3)-C(5) of the zaragozic acids. The improvement of the synthesis of a-ketoester 2.25a from an 18% overall yield to 28% while also reducing the amount of chromatography needed for the intermediates was accomplished. Efforts toward the elaboration of butenolide 2.30 revealed that oxygen nucleophiles were incompatible with the system, however this issue was effectively addressed by the use of a silane nucleophile, which was added in a Michael fashion to the butenolide 2.30 with the correct stereochemistry. While this was proof of concept for elaboration of the core system, it was unfortunate that the silane 2.71 could not be converted to the desired oxygen functionality. Additionally, efforts were made to incorporate functionality at C-6 from the beginning of the synthesis in the form of a brominated furoic acid derivative 2.90, however the Lewis acid mediated cyclization of this species was low yielding with unknown stereochemical outcome. In addition to the studies toward the total synthesis of 7-deoxyzaragozic acid A, the total synthesis of galtamycinone (3.2) was also investigated. Although the total synthesis could not be completed, methodologies have been developed that were used to synthesize C-aryl glycosides 3.80 and 3.85 which established these methods as a viable alternative to the O C glycoside rearrangement.