Indole Diterpene Synthetic Studies. Total Synthesis of (+)-Nodulisporic Acid F and Construction of the Heptacyclic Cores of (+)-Nodulisporic Acids A and B and (−)-Nodulisporic Acid D

Abstract

A first-generation strategy for construction of (+)-nodulisporic acids A (1) and B (2) is described. The strategy entails union of the eastern and western hemisphere subtargets via the indole synthesis protocol developed in our laboratory. Subsequent elaboration of rings E and F, however, revealed the considerable acid instability of the C(24) hydroxyl, thereby preventing further advancement. Nonetheless, preparation of the heptacyclic core of (+)-nodulisporic acids A and B, the total synthesis of (+)-nodulisporic acid F, the simplest member of the nodulisporic acid family, and elaboration of the heptacyclic core of (-)-nodulisporic acid D were achieved.

Total synthesis of architecturally complex indole terpenoids: strategic and tactical evolution

“…Following a cyclization sequence involving 69 via mesylation/cyclization, we arrived at the desired indole core 70 . A late stage Suzuki-Miyaura cross coupling 63 and deprotection then completed the first total synthesis of (+)-nodulisporic acid F. 64,65…”

Discovery of an Acid-Promoted [3+2] Cyclodimerization of 3-Vinylindoles and the Development of a General Lewis Acid Catalyzed Process

“…A hetero thiophenyl compound also yielded the corresponding cycloadduct efficiently (Table 1, entry 5), overall demonstrating the new cycloaddition process to be general for 2¢-aryl-substituted 3-vinylindoles. 9 the lecanindoles, which are potent progesterone receptor agonists, 10 and terpendole E which is a cytostatic kinensin spindle protein inhibitor. 11 13a the reaction of allylic cations with electron-rich alkenes, 13b and the transitionmetal-catalyzed addition of allylic diradical reactive intermediates generated in situ to alkenes.…”

“…Other bioactive cyclopenta[b]indoles, include yuehchukene, 5c,7 which possesses estrogenic and anti-implantation activity, and kopsane 8 alkaloids that display inhibitory activity against choline receptors. More recent examples include the insecticidal nodulisporic acids,9 the lecanindoles, which are potent progesterone receptor agonists,10 and terpendole E which is a cytostatic kinensin spindle protein inhibitor 11. While many examples of heteroatom-containing [3+2] cycloadditions have been exploited in alkaloid synthesis, 12 all-carbon intermolecular [3+2] cycloadditions are rare.…”

(S)-1-Amino-2-methoxymethylpyrrolidine

“…Enders' SAMP hydrazone method is utilized in Smith's total synthesis of nodulisporic acid A, a potent insecticide. 46, 47 The keto-SAMP hydrazone is treated with t-BuLi to give the corresponding aza-enolate that undergoes a diastereoselective aldol reaction with a functionalized aromatic aldehyde (Ar-CHO). Ozonolysis of the C=N double bond furnishes the desired β-hydroxyketone for the synthesis of nodulisporic acid A (eq 35).…”