Total synthesis of proanthocyanidin A1, A2, and their stereoisomers.
The first novel stereoselective synthesis of naturally occurring A1 (1) and A2 proanthocyanidins (2) has been achieved. The key synthetic steps involved (a) the formation of a coupled product (13 or 14) between an open chain C-ring C-4 hydroxyethoxy analogue of either (+)-catechin or (-)-epicatechin with 5,7,3',3'-tetra-O-benzyl-(+)-catechin/-(-)-epicatechin in the presence of bentonite clay K-10, (b) removal of benzyl protecting groups under mild catalytic hydrogenation conditions to form the desired A-type compound in situ as a mixture of diastereomers via ketal/oxonium ion/carbonium ion formation, and (c) separation of the diasteromers via silica gel column chromatography. The structures of A1 and A2 proanthocyanidins were unequivocally established by analytical comparison to the natural products. Following this methodology, an additional six diastereomers of proanthocyanidins A1 and A2 have been synthesized. A plausible mechanism for the formation of the A-type linkage in proanthocyanidins has been proposed.
Pradeep K
PK
Sharma
‡MARS Incorporated, 6885 Elm Street, McLean, Virginia 22101, United States.
Leo J
LJ
Romanczyk
Leelakrishna
L
Kondaveti
Bollu
B
Reddy
Jeeva
J
Arumugasamy
Richard
R
Lombardy
Yanni
Y
Gou
‡MARS Incorporated, 6885 Elm Street, McLean, Virginia 22101, United States.
Hagen
H
Schroeter
D002392:Catechin / Q000737:chemistry*; D015394:Molecular Structure; D044945:Proanthocyanidins / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D044945:Proanthocyanidins; C473739:proanthocyanidin A1; C473740:proanthocyanidin A2; D002392:Catechin