Studies Towards the Total Synthesis of Di- and Sesterterpenes with Dicyclopenta[a,d]cyclooctane Skeletons. Three-component Approach to the A/B Rings Building Block

Abstract

Sesqui- and sesterterpenes of ophiobolin and fusicoccin families are important synthetic targets because of complexity of structure and potentially useful physiological activities, including anti-tumor activity. A synthesis of versatile building blocks for these terpenoids is described. Cyclopenta[8]annulene rings system with properly dislocated substituents was constructed using as key steps ring closing metathesis reaction and Wagner - Meerwein rearrangement. Ring closing metathesis reaction leading to cyclopenta[8]annulene was studied in detail.

Ionic Liquid-Promoted Wagner–Meerwein Rearrangement of 16α,17α-Epoxyandrostanes and 16α,17α-Epoxyestranes

“…The Lewis acid-catalyzed rearrangement of similar epoxides was shown to lead to 17β-methyl-Δ 13 -18-norsteroids − ,− that were obtained as side products 3a , b and 7a , b here. As interaction of the C2 proton of the imidazolium cation of the ionic liquid and the oxygen atom of an epoxide ring was detected by NMR methods by Yang et al, the formation of products 3a , b and 7a , b may follow a similar mechanism (Scheme ) to the Lewis acid-induced rearrangement.…”

“…The same reaction took place even in the absence of nucleophilic reagent. The product was identified as a 17-methyl-18-nor-5α-androstan-16-one that is an unusual rearrangement product of 1a , as the usual acid-catalyzed reaction of similar compounds was shown to lead to 16α-hydroxy-Δ 13 -18-norsteroids. − ,− The structure of 2a was proved by various spectroscopic methods including 2D NMR techniques (see below).…”

“…The use of 17β-alkyl-16α,17α-epoxides usually led to the 17α-substituted 16α-hydroxy-17β-methyl-Δ 13 -18-norsteroids. At the same time, Wicha and co-workers obtained a mixture of 16α-hydroxy-Δ 12 and -Δ 13 compounds in the reaction of a 17β-H 16α,17α-epoxide and AlCl 3 . Recently, a Bi(OTf) 3 -catalyzed rearrangement was shown to result in a mixture of isomeric 16α- and 16β-hydroxy derivatives, while in the presence of an acylating agent the reaction afforded the 16α-acyl product selectively …”

Construction of Eight-Membered Carbocycles with Trisubstituted Double Bonds Using the Ring Closing Metathesis Reaction

“…Once more, rearrangement occurred at a higher temperature. Wicha has presented an excellent review that includes their results [ 47 ].…”

Screening and identification of insertion mutants from Bipolaris eleusines by mutagenesis based on restriction enzyme-mediated integration

“…One of the major limitations of the use of ophiobolins as pesticide agents is their low yield under the common solid and liquid fermentation conditions used to produce the bioherbicide fungus inoculum. Although a number of studies on synthesizing ophiobolins have been conducted (Michalak et al ., ; Noguchi & Nakada, ) and the enantioselective total synthesis of ophiobolin A was proceeded by a convergent approach (Tsuna et al ., ), the complex structure of ophiobolin A makes commercial‐scale production uneconomical. To improve the yield of ophiobolin production by the bioherbicide agent H. gramineum , potent isolates were mutagenized with UV light (Zhang et al ., ) and protoplast fusion (Zhang et al ., ).…”