Preparation of (S)‐2‐Methylbutylamine and Synthesis of Chiral Isoleucine and Alloisoleucine

Abstract

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.

Conformation of cyclo‐(D‐phenylalanyl‐trans‐4‐fluoro‐D‐prolyl)

“…We maintained assignments of the H i and HE chemical shifts the same as those for 2, because of a great similarity of the spectra of both compounds 1 and 2 [compare Tables 1 and 2 in Ref. (28) with the data in Table 5, this work]. The analysis revealed a predominance of the EN form in the Phe residue of 1' both in CDCl, and C,D, (71% and 55%, respectively).…”

PREPARATION OF RACEMIC 2r‐CARBOXY‐TRANS, TRANS‐3, 4‐DIDEUTERO‐PYRROLIDINE (DL‐TRANS, TRANS‐3, 4‐DIDEUTERO‐PROLINE) AND UNAMBIGUOUS ASSIGNMENT OF PROTONS IN THE 1H N.M.R. SPECTRUM OF PROLINE

“…The present study shows that the synupfield rule is at fault and that the original assignments are in fact correct. We have shown recently that in cis-4-fluoroproline-containing DKP's the expected synclinal upfield effect of an F-substituent also is not corroborated in these derivatives (Anteunis & Cuypers, 1979). DISCUSSION (See also Scheme.…”

“…spectrum, representing spin systems with highly diagnostic coupling constants. Among these DKP's the case of c/Pro, Aib/ (Aib, a-aminoisobutyric acid) is of special interest because in the solvent system CDC13:C6D6 (60:40) and at high field strengths, none of the patterns overlap Anteunis & Liberek, 1978).…”

Conformation of the eosinophil chemotactic tetrapeptides and analogues in dimethyl sulfoxide.

“…Furthermore, the glycine vicinal couplings (Table 2) Further evidence for a highly favoured solution conformation for the Ma3 analogue in DMSO-d6 is given by the large chemical shift difference between the Gly Ha2 and Ha3 methylene proton multiplets (Table 1). Such non-equivalence was found in peptides with well characterized bend structures (13,33), although a literature review has cited several other possible reasons for glycine methylene proton inequivalence (34).…”