Synthesis of hongconin and related naphtho[2,3-c]pyrans

Abstract

The naphtho[2,3-c]pyran occurs frequently in nature as derivatives of the 5,10 quinones. The most common examples include the eleutherins and protoaphins. These naturally occurring compounds have been found to possess antibiotic activity through the process of bioactivation. The possibility of appropriately substituted compounds functioning as bioreductive alkylating agents provides a logical model that has a great deal of predictive power. The thesis deals with the synthesis of some naphtho[2,3-c]pyrans to be tested biologically; the challenge being to design compounds in a biologically inactive form which become activated only subsequent to an in-vivo transformation. Chapter One describes and compares a high yielding synthesis of a naphtho[2,3c] pyran, hongconin, to a previous route.,a Racemic hongconin (29) has been synthesised from adduct (43) formed by reaction between 1-methoxycyclohexa1,4- diene (41) and 1,4-benzoquinone (42). The key steps includes Fries and Claisen rearrangements, base and cerium(lVj initiated pyran ring formation, C-4 pyran ring hydroxylation and silver(ll) mediated oxidation. The target compound (29) was tested in vitro for antimicrobial activity and compared to the results obtained for isoeleutherin (2) and its 9-demethoxy analoque (30). The spectral data, melting points and yields of the individual compounds is as described in Chapter Two.