textStudies 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.Chemistry and Biochemistr
