Total synthesis of -verrucarol

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. ... 

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... 

Trost and co-workers reported their total synthesis of racemic verrucarol in 1982 [67]. Their approach, illustrated in Scheme 14, featured a ring enlargement reaction of a 6/5/5-ring system to the 6/6/5-ring system for the B/C ring construction in a later stage of the total synthesis. At the... 

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). 

Having verrucarol (454), the derivative of verrucarinic acid (465), and the half ester of ( ,Z)-muconic acid (456) all on hand, the total synthesis of verrucarin A (380) could be completed in a further five steps. Thus, verrucarol (454) was esterified first with compound 465 and second with compound 460. Then, molecule 467 was desilylated, macrolactonized under Yamaguchi conditions, and finally deprotected to achieve the natural product verrucarin A (380) (Scheme 8.17). 

Most synthetic work directed toward the macrocyclic trichothecenes has focused on the verrucarins, particularly verrucarin A (37) and verrucarin J (40). For verrucarin A there now exist two total syntheses 106, 133), starting from verrucarol (82), as well as innumerable reports on the synthesis of verrucarinic acid derivatives, a principal component of the macrocyclic ribbon (see Scheme 32). 

---