3‐Hydroxyhydantoine: Eine neue Klasse cyclisch diacylierter Hydroxylamine

Fankhauser, Péter; Brenner, M.

doi:10.1002/hlca.19700530845

Cited by 8 publications

(2 citation statements)

References 17 publications

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“…After many unsuccessful trials, the desired products were finally obtained by a new reaction. This reaction may involve a two-step mechanism (29,33): ( a ) nucleophilic substitution (Scheme IV) and (b) intramolecular cyclization (Scheme V). The yield decreases as the alkyl group becomes bulkier, primarily due to the steric hindrance that decreases or prevents the cyclization (Table I).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Antieancer Activity of Novel Cyclic N-Hydroxyureas

Chou

Beck

Khwaja

et al. 1977

Journal of Pharmaceutical Sciences

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Section: Resultsmentioning

confidence: 99%

Synthesis and Antieancer Activity of Novel Cyclic N-Hydroxyureas

Chou

Beck

Khwaja

et al. 1977

Journal of Pharmaceutical Sciences

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“…Bav., 1965, 98, 640, 3340. (23) ;12 this reacts directly with a-isocyanato-esters to provide dipeptide analogues (25), or, via its 2,4,5trichlorophenyl ester (24), with amino-components of normal peptide synthesis, to provide extended analogues (26) (Scheme 5).…”

Section: Mementioning

confidence: 99%

Polypeptides. Part XIII. Preparation of α-aza-amino-acid (carbazic acid) derivatives and intermediates for the preparation of α-aza-peptides

Dutta¹,

Morley²

1975

J. Chem. Soc., Perkin Trans. 1

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Esters and amides of several a-aza-amino-acids (carbazic acids), and intermediates of use in the introduction into peptides of a- aza-gtycyl, -alanyl, -valyl, -1eucyl. -isoleucyl, -phenylalanyl, -tyrosyl, -tryptophyl, -prolyl, -aspartyl. -asparaginyl, -glutamyl, -glutaminyl, and -pyroglutaminyl residues are described. t-Butyl 3-alkyl-or -aralkyl carbazates, obtained by catalytic hydrogenation of the corresponding hydrazones, were the most versatile intermediates ; they were converted in high yield into a-aza-amino-acid esters and amides, gave a-aza-dipeptide esters when treated with at-isocyanato-esters, and afforded ' active esters ' of N-t-butoxycarbonyl-a-aza-aminoacids when treated with 2,4,5-trichlorophenyI chloroformate.REPLACEMENT in peptides, of the a-CH groups of aminoacid residues by N has little effect on the overall polarity of the molecule and the relative spacing of side-chain residues, but would be expected to induce new chemical and biological properties by virtue of the changed conformational situation at the residue or residues concerned. Our interest over the past six years in analoguesof this type (a-aza-peptides) has led us to establish general methods for the synthesis of a-aza-amino-acid derivatives and the incorporation of a-aza-amino-acid residues into peptides. This aspect of our work is described in the present paper. Subsequent papers in the series will deal with the use of this methodology in the synthesis of a-aza-analogues of biologically active peptides and model enzyme substrates.a-Aza-amino-acid derivatives and a-aza-peptides have hitherto been little explored. Ethyl esters of a-azaphenylalanine, -alanine, -leucine, and -methionhe were prepared by Ronco et aL2 by alkylation/aralkylation of ethyl carbazate, using biacetyl for amino-protection (Scheme 1). Kurtz and Nieman found the methodReagents: see caption, Scheme 2 unattractive for the preparation of N-acetyl-a-azaphenylalanine ethyl ester preferring the ethoxycarbonylation of methyl 3-benzylcarbazate. Gante, in extensive studies: developed methods for the incorporation of aza-glycyl residues into peptides, and demonstrated that a-aza-alanine and -phenylalanine may be incorporated by selective acylation of methyl-and benzyl-hydrazine. Hess, Moreland, and Laubach prepared an analogue of bovine angiotensin I1 in which the 5-valyl residue is replaced by a-aza-valyl ; the incorporation of aza-valine involved the reaction of t-butyl-3-isopropylcarbazate with the adjacent amino-acid residue (tyrosine) as its N-carbonyl ethyl ester. Niedrich and his co-workers prepared a-aza-asparagine and aza-glycine analogues of oxytocin 6 and of eledoisin 7 octapeptide, and a-azaalanine analogues of eledoisin hexa-and penta-peptides ; the incorporation of a-aza-asparagine and -alanine involved selective acylation of hydrazinoacetamide or methylhydrazine.Our own work has shown that the most useful and versatile intermediates are t-butyl 3-alkyl-or -aralkylcarbazates (4). Carbazates of this type, suitable for the synthesis of aza-valine, -leucine, -...

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α‐Bromisocyanate

Reck

Jochims

1982

Chem. Ber.

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Isocyanate R'R'CH -NCO ( l a -j) lassen sich rnit N-Bromsuccinimid photochemisch in hohen Ausbeuten zu den a-Bromisocyanaten R'R2CBr -NCO (2a -j) bromieren. Methylisocyanat (li) reagiert zu einem Gemisch von (Tribrommethy1)isocyanat (29 und Carbonyl-bromid-isocyaniddibromid (2i'). Das Neopentylisocyanat (lj) wird zu den tautomeren Dibromisocyanaten 2j und 2j' bromiert. Die Barriere der behinderten Rotation der fert-Butylgruppe in 2j betragt AGG0 = 51 kJmol-'. Die a-Bromisocyanate reagieren rnit Kaliumrhodanid zu den a-Isothiocyanato-isocyanaten 5. Ferner werden Umsetzungen von a-Bromisocyanaten rnit Blausaure, Aminen, Harnstoffen und Alkoholen beschrieben. Mit N-Methylhydroxylamin erhalt man die Oxadiazolidinone 13. a-Bromo IsoeyanatesIsocyanates R'R'CH -NCO ( l a -j) react with N-bromosuccinimide photochemically to form abromo isocyanates R'R'CBr -NCO (2a -j) in high yields. Methyl isocyanate (li) gives a mixture of tribromomethyl isocyanate (2i) and carbonyl bromide isocyanide dibromide (2i'). Neopentyl isocyanate (lj) is brominated to the tautomeric dibromo isocyanates 2j and 2j'. The barrier to hindered rotation of the tert-butyl group in 2j amounts to AG&, = 51 kJmol-'. With potassium thiocyanate the a-bromo isocyanates form the a-isothiocyanato isocyanates 5. Reactions of abromo isocyanates with hydrocyanic acid, amines, ureas, and alcohols are described. Reaction with N-methylhydroxylamine yields the oxadiazolidinones 13. Die jungst beschriebenenPhotobromierungen von primaren und sekundaren Alkylisothiocyanaten rnit N-Bromsuccinimid (NBS) zu a-Bromisothiocyanaten lassen sich auf Isocyanate mit a-standigem H-Atom iibertragen [Gl. (l)].Bestrahlt man z. B. eine Losung von 2-Isocyanatopropionsaure-ethylester (1 b) in absol. Tetrachlorkohlenstoff, in der ein Molaquiv. frisch bereitetes NBS suspendiert ist, bei 22°C mit dem Licht einer Quecksilberhochdrucklampe, so beginnt sich alsbald das am Boden liegende NBS aufzulosen und festes Succinimid als spezifisch leichtere Schicht auf der Losung abzuscheiden. Die Reaktion ist nach 45 min beendet. Man erhalt den 2-Brom-2-isocyanatopropionsaure-ethylester (2b) als farbloses, feuchtigkeitsempfindliches 0 1 in 82% Ausbeute. Ahnlich reagieren die anderen Isocyanate 1.a-Bromisocyanate sollen nach einem neuen Ubersichtsartikel iiber a-Halogenisocyanate4) instabil und nicht isolierbar sein. Tatsachlich sind in der Literatur nur wenige a-Bromisocyanate beschrieben. (Brommethy1)isocyanat (2, R' = RZ = H) lafit sich aus Bromessigsaure-azid durch Curtius-Abbau d a r~t e l l e n~.~) .Entsprechend wurde das Benzylderivat 2f erhalten '). In anderen Fallen wurden die a-Bromisocyanate nicht isoliert 8,9). Das a-Bromisocyanat 2h schlieRlich erhielt man 10) durch Umsetzen von Benzophenonimin rnit Carbonyl-dibromid oder O~alyl-bromid~).

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3‐Hydroxyhydantoine: Eine neue Klasse cyclisch diacylierter Hydroxylamine

Cited by 8 publications

References 17 publications

Synthesis and Antieancer Activity of Novel Cyclic N-Hydroxyureas

Synthesis and Antieancer Activity of Novel Cyclic N-Hydroxyureas

Polypeptides. Part XIII. Preparation of α-aza-amino-acid (carbazic acid) derivatives and intermediates for the preparation of α-aza-peptides

α‐Bromisocyanate

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