Total synthesis of (-)-reidispongiolide A, an actin-targeting macrolide isolated from the marine sponge Reidispongia coerulea.
A stereocontrolled total synthesis of the microfilament-destabilizing cytotoxic macrolide (-)-reidispongiolide A, isolated from the New Caledonian marine sponge Reidispongia coerulea, is described. This synthesis utilizes a convergent aldol-based strategy to construct the 26-membered macrolactone, followed by the late-stage coupling of a derived aldehyde with an N-vinylformamide-containing ketone subunit to install the full side chain. Two alternative routes were examined for the introduction of the 2E,4E-dienoate region, and a complex Mukaiyama aldol coupling was used to connect the northern and southern hemispheres to install the C13 stereocenter. This constitutes the first chemical synthesis of any member of the reidispongiolide/sphinxolide family of marine macrolides and unequivocally establishes the relative and absolute configuration.
Paterson
Ian
I
University Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK. ip100@cam.ac.uk
Ashton
Kate
K
Britton
Robert
R
Cecere
Giuseppe
G
Chouraqui
Gaëlle
G
Florence
Gordon J
GJ
Knust
Henner
H
Stafford
Jonathan
J
D000199:Actins / Q000378:metabolism*; D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism
D000199:Actins; D000447:Aldehydes; D007659:Ketones; D018942:Macrolides; C476919:reidispongiolide A; C116609:3-hydroxybutanal