Stizolobic acid

When chlorinated and dehalogenated in the presence of a base, dimethyl iV-acetylstizobolate, a derivative of the nonproteinogenic stizolobic acid, afforded a derivative of the pyrrolo[3,4-h]pyran system 73 (86LA1968). 

The chemical viability of the L-dopa diol cleavage process involved in the generation of the acromelic acid C-4 substituents has been examined in a biomimetic sense by Baldwin s group in syntheses of stizolobic acid 16,22 3-(6-carboxy-2-oxo-4-pyridyl)alanine 17,22 and stizolobinic acid 1523 (Figure 5). 

The distal extradiol cleavage of L-dopa 12, catalyzed by an iron-dependent dioxygenase, gives an alanyl muconic semialdehyde derivative 18 which, on cyclization and lactol oxidation, yields stizolobic acid 16. The pyrone ring is then ammonolyzed24 to give 3-(6-carboxy-2-oxo-4-pyridyl)alanine 17 (Scheme 3). 

A biomimetic catechol cleavage reaction was carried out on dihydro-caffeic acid derivative 1922 using the iron(III)-catalyzed peracetic acid cleavage process of Pandell.25 This produced the cyclized muconic acid derivative 20 which could be transformed into pyrone 21 by treatment with hydrochloric acid. Bromination followed by azide displacement gave key intermediate 22 which could either be reduced directly to (i)-stizolobic acid 16 or ammonolyzed and then reduced to give ( )-3-(6-carboxy-2-oxo-4-pyridyl)alanine 17 (Scheme 4). 

Stizolobic acid (= 2-Amino-3-(6-carboxy-2-oxo-2H-pyran-4-yl) propanoic acid) pyranyl propionic acid)... 

The procedure given here describes the preparation and use of N-(benzyloxycarbonyl)-L-serine 0-lactone for the synthesis of a protected 0-substituted alanine, N -(benzyloxycarbonyl)-0— (pyrazoM-yl)-L-alanine. This compound occurs in watermelon seeds,9 and has been used as a histidine analog.4b Its synthesis illustrates how serine 0-lactones can provide convenient access to other 0-substituted alanines such as mimosine, willardiine, quisqualic acid, and stizolobic acid which occur in higher plants.53 10 Many previous chemical syntheses of racemic pyrazolylalanine have been published the best of these routes appear to be from acetamidoacrylic acid (94-96% yield)11 and from O-acetylserine (40-45%).4c The... 

A synthesis of the plant based amino acid stizolobic acid features an Fe(III)-catalysed cleavage of the acid (14) and subsequent rearangement of the resulting butenolide to desaminostizolobic acid (94TL6S75). 

Metabolism 3,4-D. is formed from tyrosine by means of tyrosine 3-monooxygenase (EC 1.14.16.2.) and tet-rahydrobiopterin. DOPA is a biosynthetic precursor of dopamine, noradrenaline, and adrenaline. It is used for therapy of Parkinson s disease (dopamine deficiency). Oxidation and subsequent polymerization lead to the formation of melanins. Extradiol cleavage of the benzene ring gives rise to betalamic acid, " stizolobic acid, stizolobinic acid, muscaflavin, etc. 3,4-D. is toxic for the development of certain insects and for the reproduction of the duckweed Lemna minor. ... 

Fig. 37.17. Cleavage of DOPA to produce muscaflavin, stizolobic acid, and betalamic acid (Mabry, 1977 modified and used with permission of the copyright owner, Dr. T. J. Mabry).

Saito, K., A. Komamine, and S. Senoh Further Studies on the Biosynthesis of Stizolobinic Acid and Stizolobic Acid in the Etiolated Seedlings of Stizolobium hass-joo. Z. Naturforsch. 31c, 15 (1976). 

The 0- and iV-hyterocyclic compounds muscaflavin, stizolobinic acid, stizolobic acid, and (S)-betalamic acid shown in Fig. 291 are derived from l-DOPA. The 0-heterocyclic derivatives contain still the L-alanyl side chain. 

S)-proline-betaxanthin (9-36),portulaxanthin I (9-36) containing 4-hydroxyproline residue and muscaurin (muscaaurin) I (9-37) and muscaurin II (9-38), which are derived from ibotenic and stizolobic acids, respectively. 

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