Of -verrucarol

In a one-to-one ratio the reaction of CDI with (CH3)3Si(CH2)20H gave the corresponding imidazole carboxylate (97% yield), which was used in a selective protection of verrucarol, the parent compound of mycotoxines, as follows 12403... 

In a projected synthesis of verrucarol in which the tetrahydropyranone 175 is envisioned to play a role, the lactone 176 can serve as a viable intermediate (Scheme 6)7S>. Using cyclobutanone annulation methodology, 177 becomes the required intermediate. The geminal substitution of 177 can also be recognized to derive from a spiroannulation approach as previously analyzed. 

A model study 92) showed that when the hemiacetal (268) was solvolyzed in formic acid, the bicyclic product (269) was isolated in good yield 92). This method was then used to synthesize the tricyclic nucleus of verrucarol (272)92). On reaction with pTsOH, the acetate (270) underwent rapid rearrangement to (271), which constituted part of the structural feature of verrucarol (272) 92K... 

Mono- and bi-cyclic cyclopentanes, known precursors of variety of sesquiterpenes, have been prepared by the acid-catalysed rearrangement of 1-methylcyclo-butylmethanols. An acid-catalysed rearrangement (see Scheme 77) has been found to afford a practical method for converting a bicyclo[4.2.0]octene system (221) into a bicyclo[3.2.1]octene framework (222) in a recent synthesis of verrucarol. ... 

D. B. Tulshian and B. Fraser-Reid, Studies directed at the synthesis of verrucarol from D-glucose The A-B moiety. Tetrahedron 40 2083 (1984). 

The successful synthesis of optically active 7 then led to the first synthesis of verrucarin A (8), a macrotrilactone with significant cytostatic activity. The synthesis involved esterification of the primary alcohol of verrucarol (the tricyclic fragment) with the acetate of 7 (DCC, 4-pyrrolinopyridine) and then with a protected derivative of (E, Z)-muconic acid. After deprotection (Bu4NF), lactonization was effected by the Mitsunobu procedure (7,405-406). 

The bicyclic lactone (117) has been considered as a useful synthon for the synthesis of verrucarol (118). A second synthesis of this lactone has been described (Scheme 22)7° Starting from verrucarol (118), Tamm et have appended the two requisite side-chains (119) which can be lactonized with di-(2-pyridyl) disulphide and triphenylphosphine to give tetrahydroverrucarin J (120). A recent investigation of the biosynthesis of trichodermin (121) using [l- C]acetate is in accord with an earlier result although some reassignments of certain chemical shifts have been suggested, ... 

Ishihara, J, Nonaka, R, Terasawa, Y, Shiraki, R, Yabu, K, Kataoka, H, Ochiai, Y, Tadano, K.-i, Total synthesis of (—)-verrucarol, a component of naturally occurring verrucarin A, Tetrahedron Lett., 38, 8311-8314, 1997. 

Trost also found that treatment of these cyclobutanones with sodium methoxide and diphenyl disulfide leads to in situ bisulfenylation and ring cleavage (secosulfenylation). This was applied to the total synthesis of verrucarol, a complex tetrahydrochromanone substituted at the ring junction by a hydroxymethyl substituent. The synthetic strategy twice used the cyclobutanone formation from 1-lithiocyclo-propyl phenyl sulfide and a ketone, followed by the secosulfenylation process and Baeyer-Villiger type rearrangement of cyclobutanone. Only this part of the synthesis is described in Scheme 28. 

The Barton decarboxylation procedure was used in the total synthesis of (-)-verrucarol by K. Tadano et al. The initially formed thiohydroxamic ester was decarboxylated to leave a methylene radical on the cyclopentyl ring, which was then trapped by molecular oxygen. Reductive work-up in the presence of f-BuSH finally provided the hydroxylated product. ... 

Rearrangement. An entry into the trichothecane nucleus from a fused ring portion to the bridged ring system is based on ionization of the allylic lactone that triggers a C-C bond migration. The product is a synthetic precursor of verrucarol. 

Diverse allylic stannanes have been successfully used to gain access to complicated compounds. An intramolecular thermal allylation of a ftt-formylallylstaimane was used to construct the bicyclic BC array of verrucarol (Scheme 12.5) [21]. 

As with other diazoalkanes, diazomethane reacts with alkenes to form cyclopropane derivatives (sec. 13.9.C.i).272 Reaction with aromatic derivatives leads to ring expansion to cycloheptatriene derivatives.223 Both of these reactions (addition to an alkene or arene insertion) involve generation of an intermediate carbene and addition to a jt bond they will be discussed below. Many of the reactions of diazomethane tend to be ionic in nature and are, therefore, set aside from the other diazoalkane chemistry in this section. One of the commonest uses of diazomethane itself is esterification of small quantities of acids, especially acids that are precious for one reason or another. The reaction is quantitative and gives good yields of a single product, as in Tadano s conversion of 338 to the methyl ester of 339224 in a synthesis of (-)-verrucarol. 

In the initial stage of the total synthesis of (-)-verrucarol (9) from 2, we utilized the above Knoevenagel-type intramolecular cyclization strategy for the construction of the A-ring as illustrated in Scheme 18. Hydride reduction of 2 followed by a modified Mitsunobu reaction [86] of the... 

IVIchoverroids. T. are open chain ester derivatives of verrucarol (see scirpenols) and some are biogenetic precursors of the macrocyclic tric(h)othecenes ( bac-charinoids, roridins, verrucarins) they are isolated from cultures of Myrothecium verrucaria, M. roridum, and Fusarium graminearum. The T., of which more than 20 are now known, exhibit weak or no cytotoxic properties and weak antifungal activities. Trichoverri-tone also has antibacterial activity. 

The early work on the biosynthesis of the trichothecene nucleus related to the formation of trichothecolone (101) in Trichothecium roseum and of derivatives of verrucarol (102) in Myrothecium spp. This work has been reviewed in detail (248). The more recent work has been... 

There exist just a few total syntheses of macrocyclic trichothecenes. However, all of these deal with the synthesis of verrucarol (454), a hydrolysis product of the naturally occurring verrucarin A (380). Venucarol (454) represents the sesquiterpenoid moiety of most macrocyclic trichothecene derivatives. To date, there are several syntheses of this moiety. In 1998, the most recent total synthesis was published by Tadano et al. (327). 

The synthesis of verrucarol (454) started with the a-methylated bicyclic y-lactone 437, which was synthesized in 23 steps from commercially available diacetone glucose 435 (328, 329) (Scheme 8.10). 

Scheme 8.13 Synthesis of verrucarol (454). Reagents and conditions a) Ph3P=CH2 b) TMSBr, -30°C, TBSOTf c) NBS d) TBAF e) m-CPBA f) Zn-Ag...

ScHLESSiNGER and Nugent 125) also employed the group 3 biomimetic cyclization in their benchmark synthesis of verrucarol (82). The key intermediate in their synthetic plan was the bicyclic compound (154) obtained in 10 steps from the readily available dione (153). With the C-ring... 

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