Vinylglycine

Optically pure vinylglycine derivatives 3 can be prepared by reacting lithiated (2aldol adducts 212. Hydrolysis of the adduct, followed by heating in 5N hydrochloric acid, effected ester hydrolysis and Peterson elimination to give the vinylglycine derivatives. 

In a manner similar to carbonyl compounds, thioketones react with lithiated (2,S )-2,5-dihvdro-2-isopropyl-3,6-dimethoxypyrazines to give the 2,5-trun.s-adducts 2 with the diastereomeric excess exceeding 95% 12. The adducts can be further modified to give vinylglycine derivatives12. 

The X-ray structure of [cp Ir(CNR)Cl2], CNR = l,3,4,6-tetra-0-acetyl-2-deoxy-2-isocyano-Q,, 3-D-glucosc, has been determined.428 The synthesis of chiral complexes of Ir111 with Q-amino acid anions, L-L, of general formula [cp Ir(Cl)(L-L )] (252), and their NMR spectroscopic characterization, have been detailed. The X-ray structures of (252), L-L = L-proline and [cp Ir(Cl)(L-His-OH)]Cl, His = histidine, are described.429 C-allylglycinate binds in a terdentate manner in (253), which has been characterized by X-ray diffraction studies.430 C-vinylglycinate forms complex (254). 

Anionic trivalent phosphorus reagents have also been found to be of use in the preparation of some intriguing species. For example, an approach to L-phosphinothricin and related materials has been accomplished by addition of the conjugate base of alkyl methylphos-phonites to protected L-vinylglycine species (Equation 3.31).450 The starting protected L-vinylglycine species are readily available from l-methionine and L-glutamic acid. 

Zeiss, H.J., Enantioselective synthesis of L-phosphinothricin. III. Enantio-selective synthesis of L-phosphinothricin from L-methionine and L-glutamic acid via L-vinylglycine, Tetrahedron, 48, 8263, 1992. 

The second example was the startlingly successful cross-metathesis of allyltri-methylsilane with a sterically hindered, readily isomerised vinylglycine 21 in an excellent yield and with very little isomerisation using Schrock s molybdenum... 

We have also studied the effect that moving the double bond closer to the amino acid moiety has upon the reactivity of unsaturated a-amino acids [43]. To this end, the cross-metathesis reactions of similarly protected homoallyl-, allyl-and vinylglycine with oct-l-ene were investigated under identical conditions (Eq. 25) (Table 3). 

It appears that the molybdenum catalyst is more suited to the cross-metathesis of the sterically bulky vinylglycines. The cross-metathesis reaction of a similarly protected dehydro alanine gave only recovered starting material. 

Covalent adduct of ACS with the external aldimine of L-vinylglycine with PLP... 

Schemes Model of mechanism-based inactivation of ACS by SAM (a-e) Model of mechanism-based inactivation of ACS by L-vinylglycine (l-VG) (f-g-d-e) Conversion of l-VG to a-ketobutyrate and ammonia catalyzed by ACS (f-h). Notations are as in Scheme 2. For details see text.

The hydroxylamine or vinylglycine analogues are potent inhibitors of PLP-dependent enzymes in vivo and in vitro. The hydroxylamine analogues inactivate the enzyme forming stable oximes with PLP. 

Vinylglycine was used in the reaction with dibromoformaldoxime for preparation of a biologically active bromoisoxazoline 30, prepared previously from tricholomic acid (79JA1054 80TL229). 

The product is a mixture of stereoisomers. The chloro analog, antimetabolite acivicin, was prepared in a similar manner from vinylglycine and dichlor-oformaldoxime (80JOC4817 82TL4563). /3-Isoxazolylalanines were prepared by 1,3-dipolar cycloadditions of nitrile oxides to substituted acetamidomalonates (Scheme 23) (92JMC107). 

Oxazine derivatives are formed from unsaturated AAs. Vinylglycine, after epoxidation at the double bond, yielded methyl l,3-oxazin-2-one-4-carboxylate after treatment with sodium methoxide or p-chlorophenol (90TL2291). Similarly, some alkenes react with methyl a-methoxyhippurate and cyclization occurs with BF3-Et20 (75TL3737). In sulfuric acid butyro-lactones are formed. 

Determination of the absolute configuration of 27 (a constituent of certain peptide antibiotics, the relative configuration for all racemic stereoisomers 27 - 30 was determined as summarized on p 472 and 485) by a correlation-type synthesis commencing from (S)-vinylglycine (26, R = H)203. Note that this synthesis serves only to determine the absolute configuration at C-2 of 27 (and of 29). 

This reaction has been used for preparation of the antimetabolite AT-125 (2, acivin) from (S)-vinylglycine (equation II). 

AHA= L-2-Amino-4-hexynoic acid PP= Pyridoxal phosphate AVG= Aminoethoxy vinylglycine PG= Propyl gallate... 

Carbon dioxide and Ag+ ions clearly suppressed senescence, as determined by chlorophyll loss. Aminoethoxy vinylglycine (AVG), the inhibitor of ethylene biosynthesis, also significantly suppressed senescence, as determined by preservation of chlorophyll in the leaf disks aging in the dark.Combinations of C0-, Ag ions and AVG were especially effective on preserving chlorophyll, presumably by suppressing both ethylene biosynthesis and action at the two receptor sites. After 6 days aging at 25° in the dark, the controls contained only 7% of the chlorophyll present at the start, whereas 84% of the chlorophyll was retained by the leaf disks treated with a combination of CO-, Ag and AVG. 

Unlike Af-hydroxy-2-thiopyridone, TV-hydroxy-2-selenopyridone is rather unstable and is easily oxidized. However, once photolytic treatment of O-acyl ester (53) of AMiydroxy-2-selenopyridone is carried out, the formed 2-pyridyl selenide is very useful. Thus, elimination of the selenoxides, formed from the oxidation of the selenide with mCPBA or ozone, proceeds effectively at low temperature. For example, eq. 8.23 shows the preparation of (l)-vinylglycine (56) from (L)-glutamic acid without racemization at all [70]. 

As summarized in Scheme II, PLP enzymes can catalyze replacements at the y-carbon of amino acids and eliminations of HY between C-fi and C-y. In mechanistic similarity to the aspartate-/3-decarboxylase reaction, in these processes the quinoid intermediate 1 loses a proton from C-/3, followed by elimination of an anionic group (Y ) from C-y, to generate the central intermediate PLP-vinylglycine, 4 (Scheme II). This species, the vinylogue of 1, can undergo a number of reactions. Addition of a new anionic group (Y ) and reversal of the reaction sequence constitutes the y-replacement reaction, as in cystathionine-y-synthase. On the other hand, in analogy to the protonation of 1 at C-a, 4 can be protonated at C-y,... 

It is well known that copper salts can catalyze the photocycloaddition of dienes [56]. The reaction can be very diastereoselective and useful as an access to polycyclic molecules, especially 1 - vinyl-2-allylcyclanes [57]. The reaction of vinylglycine, cinnamyl derivatives 76, and analogs is also catalyzed by Cu(I) produced in situ by the reduction of cupric triflate. The coordination of the double bonds to the copper ion during the [2 4- 2]-photocycloaddition process increase ... 

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