Biosynthesis of α-cyclopiazonic acid: stereochemical aspects ofD-ring formation

Abstract

Mevalonic acid lactone is incorporated into ct-cyclopiazonic acid with retention of the 4-pro-R-hydrogen atom; [1,2-13C2]acetate has been used as a probe to show that the cyclization of P-cyclopiazonic acid into acyclopiazonic acid involves a syn addition to the double bond.

The biosynthesis of plant alkaloids and nitrogenous microbial metabolites

“…From the results of experiments with stereospecifically labelled [4-3H]mevalonic acid [as (83)], fed together with (3RS)-[2-14C]-and (3R)-[3-14C]-mevalonic acid, it has been concluded that the (3R)-isomer of mevalonic acid is used for the biosynthesis of (86), and with retention of the 4-pro-Rproton. 48 Both results are those expected3 for the dimethylallyl unit, which is seen at its clearest in (85).…”

“…The (45) [presumably only the @)-isomer of the racemic material that was used was incorporated] was utilized without loss of tritium from C-1 . Scoulerine (47), but not tetrahydropalmatrubine (48), was incorporated, which indicates that the methylenedioxy-group is elaborated before further O-methylation, i.e. cheilanthifoline ( 49) is an intermediate.…”

“…~ The conversion of ( 85) into ( 86 The stereochemistry that is associated with the ring-closure reaction of (85) which affords (86) has been further probed in an experiment in which [1,2-13C,]acetate was used. 48 Both labelled (85) and (86) were isolated; the latter compound was converted into its C-5 epimer, in which the C-methyl groups, unlike those in (86), were distinguishable in the 13C n.m.r. spectrum.…”

iso-α-Cyclopiazonic acid, a new natural product isolated from the marine-derived fungus Aspergillus flavus C-F-3

“…Comparison of the NMR spectral data (Table 1) of 1 with those of 2 showed that 1 has the same planar structure as 2. The 1 H NMR data of 1 differed from those of 2 only in the chemical shifts of H-4 (δ H 3.78), H-5 (δ H 4.64), and H-11 (δ H 3.27), which shifted 0.10, 0.53, and 0.67 ppm more downfield than 2, respectively; and H-21 (δ H 0.85) and H-22 (δ H 1.48), which shifted 0.75 and 0.2 ppm more upfield than 2; further comparison of their CD data suggested that the only difference was the stereochemistry of C-5, viz 2 has S configuration, while 1 has R. So 1 was identified as iso-α-cyclopiazonic acid, in agreement with the reported NMR and CD data in the literature [1,8].…”

A total synthesis of (±)-α-cyclopiazonic acid using a cationic cascade

“…a-Cyclopiazonic acid (a-CPA) 1 is a major toxic principle of the fungus Penicillin cyclopium Westling, which has a world wide distribution and which is often found in stored grain and cereal. 1 Its structure was elucidated some thirty five years ago; 2 since then, its biosynthesis has been the subject of many studies 3 which have shown that b-cyclopiazonic acid 2 is its immediate biological precursor. More recently, it has enjoyed a heightened profile, by reason of its ability to specifically inhibit the Ca 2+ -ATPase of the sarcoplasmic reticulum, the very origin of its toxicity.…”