(S)-4,4-Dichloro-3-methylbutanoic acid was prepared in 51% overall yield from commercially available starting materials using an organocatalytic transfer hydrogenation to 4,4-dichloro-3-methylbut-2-enal in the key step. The (S)-dichloro acid was used as an intermediate in the first total synthesis of dysideaproline E and a diastereomer confirming the structure of the natural product.

Victorins are cyclic pentapeptide natural products isolated from the fungus Cochliobus victoriae. Using a combination of synthesis and spectroscopic methods we have assigned the geometry of the vinyl chloride residue and determined the stereochemistry of the 5,5-dichloroleucine moiety.Victoria blight is a disease of oats caused by the fungus Cochliobolus victoriae (also known as Helminthosporium victoriae) which only affects oat crops that have been derived from the oat variety Victoria. Five fractions displaying host-selective activity were isolated from the culture filtrate of C. victoriae and collectively these are known as 'victorin', 'the victorins' or HV-toxins. 1 Approximately 1-2 mg of the major metabolite, victorin C 2, was isolated from 1 L of culture broth and the NMR spectrum was complicated by the presence of different conformers. 1a,bThe cyclic pentapeptide structures of the victorins 1-5 ( Figure 1) were elucidated by extensive spectroscopic studies combined with degradation of the natural products. 1,2 The L-configuration of each amino acid residue was determined from the ORD shifts of their 2,4-DNP derivatives. 2 In addition the stereochemistry of erythro-bhydroxyleucine and threo-b-hydroxylysine residues were assigned by correlation with synthetic materials. 1,2 However, the unequivocal assignment of the stereochemistry of the two chlorinated moieties, 5,5-dichloroleucine and the a-amino-b-chloroacrylic acid requires further investigation. Herein we describe our synthetic and spectroscopic studies leading to elucidation of the geometry of the vinyl chloride moiety and stereochemistry of 5,5-dichloroleucine. Assignment of the Geometry of the a-Amino-b-chloroacrylic Acid ResidueThe 1 H NMR spectrum of the major metabolite from cultures of C. victoriae, victorin C (2) displayed a signal at d = 7.52, which was attributed to the vinylic proton, but the geometry of the vinyl chloride (highlighted in Figure 1) was not assigned by Macko, Arigoni and coworkers. 1a-c Subsequently Kinoshita, Daly, and co-workers isolated a further metabolite, victorin M (or HV-toxin M) (5), which differs from the other victorins in that the glyoxylic acid portion (R 3 , Figure 1) is replaced by glycine. 2 Following acetylation of victorin M (5) and methylation with diazomethane, they isolated methyl ester 6 as the major product as well as traces of methyl enol ethers 7 and 8, formed by displacement of the vinyl chloride (Scheme 1).Kinoshita, Daly, and co-workers 2 suggested that the geometry of the vinyl chloride in victorin M (5) was Z by comparison of the chemical shift (d = 7.68) of the olefinic proton in derivative 6 to that of (E) and (Z)-chloroacrylic acids 9 and 10 ( Figure 2). In the E-isomer 9, the b-proton is cis to the carboxylic acid and resonates at d = 7.32, similar to that observed for the signal assigned to the vinyl chloride in 6, whereas in the Z-isomer 10 the signal is upfield at d = 6.85. However, this assignment does not take into account the effect of the nitrogen of the peptide bond on the chemical s...

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