Total Synthesis of Nojirimycin SummmyAddition of the nitrone 3 (from 8 and 9) to furane, followed by oxidation with OsO, and then isopropylidenation gave the fully functionalized glycoside 12 (40% from 8) via tile glycal 10 and the hemiacetal 11. Since the glycoside cleavage of 12. leading to 13 after benzyloxycarbonylation proceeded in a mediocre yield, and since the acetolysis of 12 giving 14 (69%) was not practical, compound 12 was transformed into the hydroxy ester 17 by sequential hydrogenolysis, hydrolysis and benzyloxycarbonylation (69% overall). The hydroxy ester 17 was lactonized to give 18 (87%). Reduction of 18 first with LiBH4 (97%) and then with H,/Pd gave the key compound 20 which was transformed into nojirimycin (1) and into I-deoxy-nojirimycin (2) using prior art. The overall yield of 1 was 19.5%. Einleitung undProblemstellung. -Nojirimycin (1) wurde zuerst als Antibioticum aus Streptomyces-Stammen beschrieben [ 1-31 und spater ebenfalls aus zahlreichen Stammen der Gattung Bacillus [4] sowie unter dem Namen Moranoline aus Blattern des Maulbeerbaumes isoliert [5]. Nojirimycin wurde durch katalytische Hydrierung oder durch Reduktion mit Natriumborhydrid in das I-Desoxynojirimycin (2) ubergefuhrt [ l ] [2], das spater ebenfalls aus Bacillus-und Streptomyces-Stammen isoliert wurde [4] [6]. Nojirimycin und 1 -Desoxy-nojirimycin sind die ersten in der Natur aufgefundenen ctHeterosenn [7] [8] und besonders durch ihre starke Hemmwirkung auf (1-und /i-Glucosidasen bekannt geworden (vgl. [9] und dort zit.Lit.). Nojirimycin und 1 -Desoxy-nojirimycin wurden partialsynthetisch aus Glucose [2] [ 101 und Glucuronolacton [ 1 I] hergestellt; 1-Desoxy-nojirimycin auch aus L-Sorbose [8] [ 121 und durch eine chemisch-mikrobiologische Synthese aus Glucose [ 131. Nachdem sich die Nitrone 3 und 4 bei der asynimetrischen Synthese von Aminosauren bewahrt hatten [14], stellte sich die Frage, wie gut Monosaccharide auf ahnliche Weise totalsynthetisch zuganglich sind, namlich durch Cycloaddition von Monosaccharid-Nitronen an geeignete Olefine. In diesem Zusammenhang hat I )Korrespondenzadresse.

The 1,3-dipolar cycloaddition to ethylene of N-glycosylnitrones, formed in situ from the partially protected D-mannose-or D-ribose-oximes and various glyoxalates, gave compounds which could be transformed into both enantiomers of 3-t-butoxycarbonyl-isoxazolidine and derivatives thereof.ANALOGUES of proline possessing a heterocyclic ring other than pyrr~lidinel-~ are useful biochemical probes.* We report the asymmetric synthesis of the two enantiomers of isoxazolidine-3-carboxylic acid ('5-oxaproline') and of some of their derivatives. The synthesis is based on the 1,3dipolar cycloaddition of N-glyco~ylnitrones~ ,6 to ethylene. When the partially protected D-mannose-, or D-riboseoximes (1)6 and (2)6 were allowed to react with 1-3 to 3 mol. equiv. of the glyoxylic esterst (3), (4), or (5), in the

SummaryThe 1,3-dipolar cycloaddition of the C-t-butyloxycarbonyl-N-mannosyl-nitrone 5, formed in situ from the partially protected D-mannose-oxime 3 and the glyoxylate 4, to ethylene gave preferentially the (3S)-N-glycosyl-isoxazolidine 6 which was transformed into the 3-isoxazolidine-carboxylate (L-5-oxaproline ester) 12 and into some derivatives thereof. The (S)-configuration of 12 was proved by chemical correlation with a derivative of L-asparagine. The D-5-oxaproline ester was obtained from the corresponding N-ribosyl-nitrone 24. Two protected dipeptides containing either C-terminal-(28) or N-terminal-5-oxaproline (= Opro) (30) were synthesized. Starting from 12, the analogue 1 of captoprilm (2) was prepared and its activity as an inhibitor of the angiotensin-converting-enzyme (ACE) was examined.We have reported briefly on the asymmetric synthesis of a new proline analogue of potential biochemical interest using sugar derivatives as reagents [ 11. To determine if 5-oxaproline (3-isoxazolidinecarboxylic acid) can replace proline in biologically active compounds without loss of the biological activity, we intended to prepare the analogue 1 of captopril ((2s)

A ncw route to L-carnitine (1) based on the resolution of the triniethylanimoniuni derivative 5 is described. The enantiomeric purity of 1 is determined by 'H-NMR of its 0-acetyl hydrochloride 11 using [Eu(hfc),] aschiral shift reagent. The optical rotation of 1 with an enantiomeric purity > 99 'YO is [a]:: = -31.3" (r = 10, H,O).

Addition of dialkyl phosphites to the nitrone 6, formed in situ from the oxime 5 and formaldehyde gave the hydroxylamines 7 (86%) and 8 (88%), which reacted with p‐benzoquinone in the presence of ethylene via the C‐dialkoxyphosphonoylnitrones 9 and 10 to yield the cycloaddition products 11–14 (80–85%) with a diastereoselectivity of about 50%. The cycloaddition products were transformed into the monoisopropylidene derivatives 15–18 and the diacetates 19–22. Comparison of the NMR spectra and the specific rotations of the compounds 19–22 with those of the corresponding α‐ammo‐acid derivatives 23–26 of known configuration indicated preferential formation of the L‐isomers. The cycloaddition products were transformed in good yield into the L‐α‐aminophosphonic acids 29, 30, 36, and 39.