Structure of Brefeldin A

Abstract

On the basis of X-ray crystal structure analysis, CD. measurements, and asymmetric synthesis the absolute configuration of brefeldin A has been determined.Some years ago we reported the isolation [l] and the elucidation of the constitution 121 of brefeldin A (1) (identical with ascotoxin [3], decumbin [4] and cyanein [5]). At that time the (S)-chirality of C15, the trans connection of the two rings and the trans relationship at the conjugated double bond had been established, but the stereochemistry of the other asymmetric centers and of the isolated double bond remained to be clarified.A recent publication by SuzMki et al.[3] prompts us to describe our own results concerning relative and absolute configuration of brefeldin A, which are not fully in agreement with those of the Japanese authors. . -; H 3 0~c 0 0 c H 3 10 "COOCH, 1 R = H X = H, OH 2 R = AC X = H, OH 3 R = AC X = 0 4The NMR. spectrum of brefeldin A (1) (SO(CD,)&DCI, 7:3, 100MHz) shows signals for the protons on the isolated double bond at 5.22 and 5.60ppm (tetramethylsilane = 0) with a coupling constant of 15.5 cps, which indicates their trans relationship. The method of Horeau [6] allowed1) to specify the chirality at C4 as ( S ) in brefeldin A (1) and ( R ) in tetrahydro brefeldin A [l]. l)The resulting a-phenyl butyric acid had a = -0.091O in the case of brefeldin 4 and M = +0.087" in the case of tetrahydro-brefeldin A. The optical yield in both cases was 23%. Owing to its symmetrical position the hydroxyl group in the five-membered ring appears to be without influence on the asymmetric synthesis.

NMR structure determination of brefeldin-A, a 13-membered ring fungal metabolite

“…There is a non-optimum placement of proton coordinates in the x-ray crystallographically determined structure reported 4 for brefeldin-A, as seen by a number of small value 96-99°H-C-H bond angles. For this reason, an ab initio 9 calculated molecular model of the crystalline conformation was calculated using the x-ray crystallographically determined input structure.…”

“…3 The solid-state stereochemical features of 1 were obtained from an x-ray crystallographic study. 4 Weber et al 4 also noted that the antiperiplanar (ca 180°) relationships found for H(1)-C(1)-C(14a)-H(14a) and H(11)-C(11)-C(11a)-H(11a) in the solid-state were also retained in CDCl 3 solution, as indicated by their vicinal coupling constants of ca 9 Hz. While some additional 1 H NMR CDCl 3 data measured at 180 MHz have been reported, 5 a more complete solution-state structure still remained to be ascertained.…”

ChemInform Abstract: Nuclear Magnetic Resonance Study of the Sodium Salt of Mutalomycin, a Structural Analogue of Lonomycin.

“…Mutalomycin is a metal-complexing polyether antibiotic isolated from the structure has been established by an X-ray crystallographic study of the potassium salt, as 23,27-didemethoxy-ll-O-dernethyl-lonomycin A (Figure 1) (2). Unfortunately the atomic coordinates resulting from this X-ray analysis have not been published yet (3).…”

Distribution and Some Properties of Acid Phosphatase in the 7,12‐Dimethylbenz[a]anthraccne‐Induced Rat‐Mammary Carcinoma

“…Weber [14] has reported a significant decrease in the K , value of acid proteinase from regressing tail tissue of Xenopus larvae during spontaneous metamorphosis and induced involution in vitro and Eeckhaut [15] has reported the opposite effect on the substrate affinity of /?-glucuronidase for tails of metamorphosing tadpoles of Rana temporaria. The phenomena to our knowledge has not been reported for acid phosphatase in sex-hormone-dependent tissues.…”