Total synthesis of polycavernoside A, a lethal toxin of the red alga Polycavernosa tsudai.
[structure: see text] Two approaches to the synthesis of the aglycon 120 of polycavernoside A (1) were developed, only one of which was completed. The successful "second-generation" route assembled the aglycon seco acids 102 and 106 via Nozaki-Hiyama-Kishi coupling of aldehyde 70, prepared from methyl (S)-3-hydroxy-2-methylpropionate (72) and (S)-pantolactone (73), with vinyl bromide 71. The latter was obtained from a sequence which commenced from the silyl ether 24 of 3-hydroxypropionaldehyde and entailed cyclization of (Z)-zeta-hydroxy-alpha,beta-unsaturated ester 82. Regioselective Yamaguchi lactonization of trihydroxycarboxylic acids 102 and 106 and subsequent functional-group adjustments led to macrolactone 120, to which the fucopyranosylxylopyranoside moiety was attached. Stille coupling of the glycosidated aglycon 128 with dienylstannane 129 furnished polycavernoside A in a synthesis for which the longest linear sequence was 25 steps. The overall yield to lactone 120 was 4.7%.
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003, USA.
Paul R
PR
Blakemore
Cindy C
CC
Browder
Jian
J
Hong
Christopher M
CM
Lincoln
Pavel A
PA
Nagornyy
Lonnie A
LA
Robarge
Duncan J
DJ
Wardrop
James D
JD
White
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D002264:Carboxylic Acids / Q000737:chemistry; D003500:Cyclization; D004187:Disaccharides / Q000138:chemical synthesis*; D006031:Glycosylation; D018942:Macrolides / Q000138:chemical synthesis*; D008387:Marine Toxins / Q000138:chemical synthesis*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011422:Propionates / Q000737:chemistry; D000461:Rhodophyta / Q000737:chemistry*; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D002264:Carboxylic Acids; D004187:Disaccharides; D018942:Macrolides; D008387:Marine Toxins; D011422:Propionates; D014753:Vinyl Compounds; C121303:polycavernoside A; C005412:pantolactone; C003763:vinyl bromide; D015107:4-Butyrolactone