Lactones, preparation from amino acids

Derivatives of Y-hydroxyacetylenic acids, which are useful intermediates in the synthesis of butenolides, are prepared from propiolic acid and ester anions. Alk-2-ynoic and 2-allenic esters are prepared by the oxidation of 3,4-disubstituted 2-pyrazolin-5-ones with lead(iv) tetra-acetate in the absence and presence of BF3 respectively. Py-Unsaturated esters are produced in high yield by the palladium-catalysed decarboxylation-carbonylation of allylic carbonates. Magnesium enolates of esters react with nitriles to give (Z)-3-amino-alk-2-enoates. Enol lactones react with diethyl methoxycarbonylmethylphosphonate to give cyclic unsaturated keto-esters (Scheme 66). ... 

Fleet s group applied this procedure to prepare oxetin analogues from aldono-lactones prepared from either L-rhamnose (77) [32,33] or D-xylose (82) [32, 34], affording p-amino acid precursors type 78 and 83, respectively. Triflation of the free OH followed by nucleophilic displacement led to the preparation of oxetanes with different configuration and substitution at the p-position (Scheme 4.13). The final steps involve hydrolysis of the ester and reduction of the azide to the corresponding amine, giving monomeric structures for the synthesis of small peptides. 

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

Macrocyclic 14-membered lactams, lactones, and thiolactones 211 have also been prepared from 3-amino-l,2,5-thiadiazole-4-carboxylic acids 210 (Equation 47) <1996CHE975>. 

Amino acid synthesis.1 Optically pure amino acids can be prepared in two steps from serine, readily available as either the d- or L-enantiomer. Reaction of N-benzylserine (or of N-benzyl-N-Boc-serine) with the preformed Mitsunobu reagent in CH3CN at -55° provides the protected serine (J-lactone (2) in almost quantitative yield. The lactone reacts with lithium organocuprates (R2CuLi) to... 

The chiral lactone alcohol derivative (178)181) can be readily prepared from natural (S)-glutamic acid, the cheapest chiral a-amino acid. Lactone (178) was alkylated to yield optically active 3-substituted lactone alcohol derivatives, (179) and (180), which were intermediates in the stereoselective synthesis of various natural products 182). 

Amino lactonesThe Reformaisky reagent prepared from ethyl 2-bromo-propionate with Zn-Cu (8, 533) adds to azirines to form two isomeric products, which are converted to 4-amino lactones when treated with aqueous hydrochloric acid or HF-Py (5, 538,6,473). 

Dondoni et al. prepared a 1-hydroxyethylene peptide using a thiazole-aldehyde synthesis starting from an amino acid.[38] The aldehyde is converted into an alkanoate by Wittig alkenation and reduction of the double bond (Scheme 18). Then, removal of the tert-bu-tyldimethylsilyl group gives the unsubstituted lactone. In the last step, the lactone is alkylated using the method reported by Kleinman and co-workers. 20 ... 

Analogues of 70 have been prepared by various methods including nucleophilic displacement of triflate esters attached directly to the oxetane ring (see Section 2.05.7.2) <2001TL4247>, from xylose, 145, via the benzyl-idene-protected oxetane, 146 (Scheme 24) <2004TA2667>, or from L-rhamnose, 147, via a l,4-lactone-2-O-triflate, 148 (and key oxetane 149 (Scheme 25)) <2004TA2681>. The /3-azidoester monomers formed by these methods were converted to the /3-amino acids and subsequently to /3-peptides by reduction of the azide and ester hydrolysis. 

Pyrrolidine (39 Z = NH) and thiolane (39 Z = S) can be prepared from tetramethylene dibromide 38, and tetrahy-drofuran (39 Z = O) is obtained from the diol 40. -Hydroxy and -thiol acids (41 Z = O, S) usually cyclize spontaneously to give lactones and thiolactones 42. -Amino acids (41 Z = NH) require heating to effect lactam formation (42 Z = NH) (Scheme 31). 

Since protein and peptide syntheses are rapidly falling into the hands of organic chemists, four procedures to reach building blocks amino acids in the form of its /8-lactone Na-(BENZYLOXY-CARBONYL)-p-(PYRAZOH-YL)-L-ALANINE and the preparation of both /3-lactones, N-tert-BUTOXYCARBONYL-L-SERINE-p-LACTONE and the p-TOLUENESULFONIC ACID SALT OF (S)-3-AMINO-2-OXE-TANONE are described starting from N-tert-BUTOXYCARBONYL-L-SERINE. A useful S or R serine derivative, 1,1-DIMETHYLETHYL (S) or (R)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATEis described followed by the improved preparation of N-(BENZYLOXY-CARBONYD-L-VINYLGLYCINE METHYL ESTER, an important intermediate as well as an important substance in biological processes. 

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