Synthetic studies toward the CD spiroketal of spongistatins

Starting from the readily available meso-methylenedi(8-oxa-3-oxobicyclo[3.2.1]hept-6-en-1-yl) (1), meso-1,1'-methylidene [(4R,4'S,6R,6'S)-4,6-dioxycyclohept-1-en-1-yl]tetrasilylethers (7, 8) were obtained and transformed into all-syn 1,3,5,11,13,15-hexahydroxypentadeca-7,9-dione derivatives (9, 10). The conversion of these intermediates into spiroketals was not met with success. An alternative strategy based on the sequential and stereoselective functionalization of 1 afforded a 1-(1,3,5,7-tetrahydroxyoctyl)cyclohept-1-ene-4,6-diol derivative ((+)-15, 94 % ee). Ozonolysis of the cycloheptene moiety of (+)-19 provided equatorial/axial spiroketal (+)-21 ((+)-(2R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-[(2S,4S,6R,8S,10S)-10-{[tert-butyl(dimethyl) silyl]oxy}-4-hydroxy-8-(2-hydroxyethyl)-1,7-dioxaspiro[5.5]undec-2-yl]butan-2-yl 4-methoxybenzoate). Pivaloylation of its primary alcohol moiety and Meerwein's methylation of the remaining secondary alcohol unit furnished (−)-24, a potential precursor of a ketal-isomer of the CD fragment found in spongistatins 1 and 2.


Published in:
European Journal of Organic Chemistry, 1895-1903
Year:
2010
Publisher:
Wiley-Blackwell
ISSN:
1434-193X
Keywords:
Laboratories:




 Record created 2010-03-23, last modified 2018-03-17

n/a:
Download fulltext
PDF

Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)