Abateact.A four-atop ayntheaia (45 8 total yield) of a mixture of chiral pure Kiaoleucine and Q-alloisoleucine ia reported, via a route compriuing an odic oxidation of suitable acylamide precuraora. Efficient preparations for (~9-2-methylbutylamine from the cheap parent (s)-alcohol are deacribed. Introduction.We have in the paat explored (1) the possibilities to prepare amino acid. from the cotreaponding decarboxylated amines following a four-atop aequence exiating in (i) acylation of the amine t(ii) anodic oxidation of the acylm i n e (ECO)) (iii) nucleophilic substitution of the oxygrouping by the nitrile function using trimethylsilyl cyanide (TI4S-CN)t and (iv) total hydrolyaia (SCEEnE 1).We pceaent here the case whereby a mixture of &-Ile and _p--Ilr is obtained in 45 8 total yield by following this reaction sequence. The starting chiral (S)-2-wthylbutylamine was prepared by aevecal routes from the corresponding chiral, commercially available (s)-alcohol.Organic electrochemical reactions are becoming today popular, the reaaon originating from the high aelectivity that can often be reached in functionalirationa, and the eaay way to achieve many oxidative/raductive transformations with laboratory-friendly devicea (often open and undivided electrochemical cells). Furthermore moat of these reactions are easily upscaled, economically attractive, and clean. The Ross-Bberson-Nyberg methoxylation/acetoxylation of amides (2) is such an example for which aimple Present addresses: 'BOLVAY c Cia, Rue de Ranab-k 310, 8-1120 Brusael .-5 4 5 -how-made instrumentation (1 ) suffices. fuuaaum.varied some paraaeters for the different steps I to 4.In following the reaction path presented in SCBEUE 1, we have first 1: We have considered as protective groupings some that can easily be prepared in good yields, e.g. (i) by formylation (Prot -CBO; reagent ethyl formate), (ii) acetylation (Prot -COCB3; reagent acetic anhydride), (iii) trifluoroacetylation (Prot -COCF3; reagent sodium trifluoroacetamide reacted on 2-methylbutyl broaide), (iv) methyloxycarbonylation (Prot -COOne; Schotten-Baumann with methoxycarbonyl chloride) and (v) tosylamidocarbonylation (Prot -CONRToe; reagent p-tosyl isocyanate). Second best yield. were obtained for the formylderivative (89 t ) , which is the best choice in the subsequent ECO step, while isocyanidation, although proceeding with quantitave conversion, gives an amide that can not be oxidized anodically.

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The 'H (at 300 MHz) and 13C nuclear magnetic resonance spectra of virginiamycins S and S4 and vernamycin Bcc have been unravelled and analyzed. Together with model building and theoretical considerations, this allows the detailed description of their solution conformations. The depside bond can rotate and gives to the backbone some conformational mobility. The orientation of the depsicarbonyl bond depends on the surrounding. Apparent discrepancies between the different methods that are applicable for the disclosure of the nature of peptide H-bonding, have found a rational explanation Virginiamycin S, virginiamycin S4 and vernamycin Ba are closely related cyclic hexadepsipeptide antibiotics, and their constitutions are well established [l -31. All the residues (Fig. 1) are in the L-configuration, except aminobutyric acid (D-Abu).A spatial form has been proposed [4] for virginiamycin S and other cyclic peptide antibiotica in water, by emphasizing the optimal interaction between the polar peptide and ester bonds with the hexagonal oxygen pattern of the water structure, but none of these conformations have been corroborated by later experimental evidence [5]. Part of a 220-MHz proton

Cyclic b-amino acids, homoproline, homopipecolic acid and 3-carboxy-methylmorpholine were obtained in high enantiomeric excesses by transition metal-catalyzed asymmetric hydrogenation of cyclic b-acylamino-alkenoates. These compounds were synthesized by a thio-Wittig reaction on N-protected thiolactames.The synthesis of conformationally constrained amino acid derivatives has recently received much attention due to their ability to act as conformational probes when incorporated into peptides and peptidomimetics. 1 Among them, optically active b-amino acids, although of less importance than the parent a-amino acids, are crucial structural units of numerous biologically active and natural products. 2 Various methods are available for the synthesis of linear compounds of this series by both asymmetric synthesis and enzymatic resolutions. 3In contrast, there are few methods available for the asymmetric synthesis of cyclic b-amino acids. Some methods are known for the b 2,3 -acids. 4 For the b 3 -acids, ArndtEistert homologation of (S)-proline has been used to access to homoproline 5 and homopipecolic acid. 6 More recently, two general approaches to five-and six-membered cyclic b 3 -amino acids have been disclosed using diastereo-controlled Michael additions of chiral amides to a,b-unsaturated esters followed by intramolecular ringclosure 7 and diastereoselective reduction of the resulting chiral b-enamino esters. 8Although linear b-amino acids may be obtained in high enantiomeric excesses by asymmetric hydrogenation of b-(acylamino)acrylates, 9 to the best of our knowledge, only the synthesis of homoproline by enantioselective hydrogenation has been reported until now. 10In this paper, we wish to describe a novel and efficient synthesis of N-protected homoproline, homopipecolic acid and 3-carboxymethylmorpholine by transition metalcatalyzed hydrogenation of cyclic enamido esters.It is well known that the use of bidentate substrates is generally required to achieve highly enantioselective metal-catalyzed hydrogenations. Compounds 1-4 fit well with such requirement; they were then considered as substrates for enantioselective hydrogenations (Scheme 1). Scheme 1In contrast with the linear b-acylamido acrylates the preparation of which is well known, the cyclic analogs are of a more difficult access. The synthesis of non-protected Zenamino esters by addition of a Meldrum acid salt to a lactime ether was previously described by Lhommet et al. 11 However, such a method is not general. Only the fivemembered cyclic derivative 1 may be obtained by direct acylation of the nitrogen atom with acetyl chloride. The six-and seven-membered ring enamino esters are always acylated in position a to the ester function. Consequently, we have then developed an alternative method based on a thio-Wittig condensation 12 to access to the required compounds. The N-protected thiolactames prepared by thiolation of the corresponding lactones followed by protection of the nitrogen atom were reacted with a Wittig reagent to give mainly the E-isom...