Acids clavicipitic

Hegedus synthesis of ( )-clavicipitic acid //-acetyl methyl ester culminated in the Pd-induced cyclization of 238 to 239, the latter of which was reduced to the target mixture [251], Substrate 238 was prepared via a Heck reaction with the corresponding 4-bromo compound 223 and 2-methyl-3-buten-2-ol (83%). The cyclization also occurs with tosic acid (97%). 

In a related approach, Murakami synthesized clavicipitic acid and costaclavine [79], and later extended this chemistry to a synthesis of chanoclavine-I featuring the intramolecular Heck vinylation 240 to 241 [266], The corresponding enone failed to cyclize under these conditions. Noteworthy is that radical cyclizations, which often compete successfully with Heck reactions, were poor in this system. 

Kozikowski et al. have described a synthesis of clavicipitic acids where a key step involved preparation of the imine (202).112 Azide cyclization at 190 C presumably afforded a triazoline which, however, was nonisolable affording (202) in 62% yield. 

Some H NMR data for ergot derivatives of differing types— paspaclavine [360], (222) iV-methyl-4-dimethylallyltryptophan [361], (223) and the TV-acetyl methyl ester of clavicipitic acid [362] (224)— are shown in the structures. 

The usefulness of Pd-catalysed reactions is demonstrated amply in the total synthesis of clavicipitic acid [76]. The first step is intramolecular aminopalladation of the 2-vinyltosylamide 92 with Pd(II) to give the indole 93. Then stepwise Heck reactions of the iodide and bromide of 94 with two different alkenes 95 and 96 in the absence and presence of a phosphine ligand give 97. In the last step of the synthesis, the intramolecular aminopalladation of 97 with a catalytic amount of Pd(II) gives the cyclized product 99. It should be noted that the aminopalladation is a stoichiometric... 

Clavicipitic acid (129) (naturally occurring as a mixture of C-10 epimers) has been identified as a metabolite which is at a shunt from the main line of... 

Clavicipitic acid (129) was found to be formed from the intact skeleton of tryptophan and from mevalonate. Tritium at C-5 in samples of labelled mevalon-ate was retained at an abnormally high level (at C-10) of (129). The reason for this is not clear. 

The revised structure for clavicipitic acid, suggested earlier by King etal.,44a has been confirmed, and the stereochemistry elucidated, by X-ray crystal-structure analysis.446 The major component of the naturally occurring mixture that constitutes clavicipitic acid was obtained pure by t.l.c. on silica gel, and proves to have the (55,10/ ) stereochemistry depicted in (53). The minor component of the mixture is presumably the (55,105)-diastereoisomer. It should be noted that, at present, the absolute configuration of clavicipitic acid rests only on its biogenetic derivation from L-tryptophan.446... 

From the culture filtrates of two different Claviceps species, strain SD 58 and C. fusiformis, strain 139/2/lG, a new amino acid was isolated, named clavicipitic acid, (C16H18N202 mp 262°). 

Ergot Alkaloids.—The enzyme which catalyses the first step in ergot alkaloid biosynthesis, namely the conversion of tryptophan into dimethylallyltryptophan (126),110 has been isolated from a Claviceps species and characterized.111 The biosynthesis of clavicipitic acid (127) may be a major alternative to the synthesis of other ergot metabolites, and further results in a study112 of an enzyme from C. purpurea which catalyses the formation of clavicipitic acid (127) from (126) have been published.113... 

We end this section with a synthesis of N-acetyl clavicipitic acid methyl ester, an ergot alkaloid, by Hegedus. The power of orga no-transition-metal chemistry is illustrated in five steps of this seven-step process. Each of the organometallic steps catalysed by Pd(0) or Pd(II) has been described in this chapter. The overall yield is 18%, a good result for a molecule of such complexity. 

Some effected the coupling of phenyl-, 2-fuiyl-. and 1-hexenylboronic acids with 4-thallated indole-3-carboxaldehyde (Pd(OAc),/DMF) to give 4-substituted 3-formylin-doles [148]. Regioselective thallation of indole-3-carboxaldehyde is achieved using thallium tris-trifluoroacetate in 77% yield. Indole 129, which is available by the Buchwald zirconium indoline synthesis, was used by Buchwald to synthesize 130 via a Suzuki protocol [149]. Boronate ester 130 is prepared by the hydroboration of3-methyl-1-butyne with catechol borane. Indole 131 had been used in earlier studies to synthesize the clavicipitic acids. 

Hegedus synthesis of ( )-clavicipitic acid jV-acetyl methyl ester culminated in the... 

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