ABSTRACT
Spiroviolene is a spirocyclic triquinane diterpene produced by Streptomyces violens. Recently, a biosynthetic pathway that includes secondary carbocation intermediates and a complicated concerted skeletal rearrangement was proposed for spiroviolene, based upon careful labeling experiments. On the basis of density functional theory (DFT) calculations, we propose a revised pathway for spiroviolene biosynthesis, involving a multistep carbocation cascade that bypasses the formation of unstable secondary carbocations by breaking the adjacent C-C bond to form a more stable tertiary carbocation (IM3) and by Wagner-Meerwein 1,2-methyl rearrangement (IM7).
Subject(s)
Spiro Compounds/metabolism , Streptomyces/chemistry , Density Functional Theory , Molecular Conformation , Spiro Compounds/chemistry , Streptomyces/metabolismABSTRACT
Some experimental observations indicate that a sequential formation of secondary (2°) carbocations might be involved in some biosynthetic pathways, including those of verrucosane-type diterpenoids and mangicol-type sesterterpenoids, but it remains controversial whether or not such 2° cations are viable intermediates. Here, we performed comprehensive density functional theory calculations of these biosynthetic pathways. The results do not support previously proposed pathways/mechanisms: in particular, we find that none of the putative 2° carbocation intermediates is involved in either of the biosynthetic pathways. In verrucosane biosynthesis, the proposed 2° carbocations (II and IV) in the early stage are bypassed by the formation of the adjacent 3° carbocations and by unusual skeletal rearrangement reactions, and in the later stage, the putative 2° carbocation intermediates (VI, VII, and VIII) are not present as the proposed forms but as nonclassical structures between homoallyl and cyclopropylcarbinyl cations. In the mangicol biosynthesis, one of the two proposed 2° carbocations (X) is bypassed by a C-C bond-breaking reaction to generate a 3° carbocation with a C=C bond, while the other (XI) is bypassed by a strong hyperconjugative interaction leading to a nonclassical carbocation. We propose new biosynthetic pathways/mechanisms for the verrucosane-type diterpenoids and mangicol-type sesterterpenoids. These pathways are in good agreement with the findings of previous biosynthetic studies, including isotope-labeling experiments and byproducts analysis, and moreover can account for the biosynthesis of related terpenes.
ABSTRACT
We present the first synthesis of air/moisture-stable λ3-bromanes (9 and 10) by using a cyclic 1,2-benzbromoxol-3-one (BBX) strategy. X-ray crystallography and NMR and IR spectroscopy of N-triflylimino-λ3-bromane (12) revealed that the bromine(III) center is effectively stabilized by intramolecular R-Br-O hypervalent bonding. This strategy enables the synthesis of a variety of air-, moisture-, and benchtop-stable Br-hydroxy, -acetoxy, -alkynyl, -aryl, and bis[(trifluoromethyl)sulfonyl]methylide λ3-bromane derivatives.
ABSTRACT
We report the first stereoselective synthesis of stable (E)- and (Z)-ß-chlorovinyl-λ3-chlorane via direct mesitylation of 1,2-dichloroethylene with mesityldiazonium tetrakis(pentafluorophenyl)borate under mild reaction conditions. The structure of the (E)-vinyl-λ3-chlorane was established by single-crystal X-ray analysis. Because of the enormously high leaving group ability of the aryl-λ3-chloranyl group, vinyl-λ3-chloranes undergo not only SNVσ-type reaction with extremely weak nucleophiles such as perfluoroalkanesulfonate, iodobenzene, and aromatic hydrocarbons but also coupling with phenylcopper(I) species.
