Patent ID: 7763740
Filing Date: 2010-07-27
Classification: C07C,C07D,C09B

Abstract:
1. A process for preparing a mumbaistatin derivative of formula (I) or a salt thereof wherein: R1 and R2 are independently H, (C R3, R4 and R5 are independently OH, O—(C R6 is OH, halogen, (C X1 and X2 are independently O, NH, N(C m, n, q and r are independently 0 or 1; comprising (1) reacting a compound of formula (II) wherein Y is a leaving group selected from the group consisting of Hal, OTs, OTf and OMs, with a compound of formula (III), wherein X is an electron-pushing group and R′ is (C 1 -C 6 )-alkyl or [(C 1 -C 6 )-alkyl] 3 silyl, in a [2+4]cycloaddition, and subsequently reacting with a suitable acid to give a compound of formula (IV) wherein R″ is H or (C 1 -C 6 )-alkyl; (2) halogenating the compound of formula (IV), or an etherified or acylated compound thereof when q is 1 and R″ is H, to give a compound of formula (V), wherein the etherified compound is prepared by etherifying the compound of formula (IV) with a (C (3) reacting the compound of formula (V) with an organometallic compound (VI) wherein M is Sn[(C 1 -C 6 )-alkyl] 3 , B(OH) 2 , B(OR) 2 , BF 3 − , ZnHal or MgHal, and (OR) 2 is [O—(C 1 -C 6 )-alkyl] 2 or a 1,2-vicinal diol, in the presence of a transition metal catalyst, to give a compound of formula (VII), and then oxidizing the compound of formula (VII) to give a compound of formula (VIII), or reacting the compound of formula (V) with an organometallic compound of formula (VI′) wherein M is as defined for compound (VI) and Z is O—(C 1 -C 6 )-alkylene-O, in the presence of a transition metal catalyst, to give a compound of formula (VII′), and then hydrolyzing the compound of formula (VII′) with a suitable acid to give a compound of formula (VIII), or when X2R2 is OH, esterifying the compound of formula (V) with the compound (VI) to give a compound of formula (VII″), converting the compound of formula (VII″), in the presence of a transition metal catalyst, into a compound of formula (VII′″), hydrolyzing the compound of formula (VII′″) under a basic or acidic condition to give a compound of formula (VII) wherein X2R2 is OH, oxidizing the compound formula (VII) to give a compound of formula (VIII) wherein X2R2 is OH, and optionally converting the compound of formula (VIII) wherein X2R2 is OH into a compound of formula (VIII) wherein X2 is O, NH, N(C 1 -C 6 )-alkyl or S, and R2 is H, (C 1 -C 6 )-alkyl or benzyl, provided that X2R2 is not OH; (4) reacting the compound of formula (VIII) with a compound of formula (IX) to give a compound of formula (X), (5) converting the compound of formula (X) into a compound of formula (XI) by hydrogenating the triple bond to a single bond and removing the [(C (6) optionally oxidizing the compound of formula (XI) to give a compound of formula (XII), (7) oxidizing the compound of formula (XI) or the compound of formula (XII) to give the compound of formula (I) wherein X1R1 is OH, and (8) optionally converting the compound of formula (I) wherein X1R1 is OH into the compound of formula (I) wherein X1 is O, NH, N(C