A detailed account of the de
velopment of a general strategy for synthesis of the C-19 methyl-substituted alkaloids including total synthesis of 19(
S),20(
R)-dihydroperaksine-17-al (
1), 19(
S),20(
R)-dihydroperaksine (
2), and peraksine (
6) is presented. Efforts directed toward the total synthesis of macrosalhine chloride (
5) are also reported. Important to success is the sequence of chemical reactions which include a critical haloboration reaction, regioselecti
ve hydroboration, and controlled oxidation (to pro
vide sensiti
ve enolizable aldehydes at C-20). In addition, the all-important Pd-catalyzed 伪-
vinylation reaction has been extended to a chiral C-19 alkyl-substituted substrate for the first time. Synthesis of the ad
vanced intermediate
64 completes an impro
ved formal total synthesis of talcarpine (
26) and pro
vides a starting point for synthesis of
macroline-related alkaloids
27鈥?b>31. Similarly, extension of this synthetic strategy in the ring A oxygenated series should pro
vide easy access to the northern hemisphere
32b of the bisindoles angustricraline, alstocraline, and foliacraline (Figure
4).