Methoxy-D-tryptophan

The total synthesis of (-)-fuchsiaefoline was accomplished in the laboratory of J.M. Cook using the Larock indole synthesis to prepare the key precursor 7-methoxy-D-tryptophan in enantiopure form. The propargyl-substituted Schollkopf chiral auxiliary was reacted with 2-iodo-6-methoxyaniline in the presence of 2 mol% Pd(OAc)2 to give the expected indole in good yield. Interestingly, the Bartoli indole synthesis gives /-substituted indoles only in moderate yield. 

Edwankar et al. reported the regio- and stereocontroUed total synthesis of the bisphenolic, bisquatemary alkaloid (f)-(+)-dispegatrine (193) (Scheme 9). In this synthesis, 5-methoxy-D-tryptophan ethylester (194) was con-... 

The synthesis of 11-methoxymacroline (254) began with Na-methyl-6-methoxy-D-tryptophan ethyl ester (255) (obtained from p-methoxy-iodoa-niline) (Scheme Ester 255 was converted into 11 -methoxyaftinisine... 

Following a similar route. Wearing and Yu et al. also synthesized (—)-ll-methoxy-17-epi-vincamajine (298) from (- -)-Na-methyl-16-ep -gardneral (280) in eight steps (Scheme 24). " In this synthesis all the steps were similar to those used for the synthesis of (—)-vincamajinine (291), except the Dess—Martin periodinane oxidation of the diol intermediate could be achieved in one pot to afford the P-oxoaldehyde in 65% yield. Overall (—)-ll-methoxy-17-ep/-vincamajine (298) was obtained in 8.4% yield in 14 reaction steps (from Na-methyl-6-methoxy-D-tryptophan). 

The first asymmetric total synthesis of the dimeric indole alkaloid (T)-dispegatrine (51) was accomplished by Cook (Scheme 1). Initially, (T)-lochnerine (52), the monomeric part of 51, was synthesized from 5-methoxy-D-tryptophan ethyl ester (53) via a nine-step operation that included the enolate-mediated palladium-catalyzed cyclization of vinyl iodide 54 as the key reaction. Thus-obtained 52 was treated with thaUium(lll) acetate (0.65 equiv) and BF3 Bt20 (3.0 equiv) at —40 °C to — 10°C to... 

The synthesis of the 10-methoxytetracyclic ketone 353 (Scheme 26) started from the readily available 3-methyl-5-methoxyindole 355, which after Boc protection, was brominated, and then condensed with the anion of the Schollkopf auxiliary 356 (from l-valine). Removal of the Boc-protecting group, followed in succession by A -methylation and hydrolysis, gave the required A -methyl-5-methoxy-D-tryptophan ethyl ester 357, which was then transformed into the key 10-methoxytetracyclic ketone 353, via N-benzylation, Pictet-Spengler condensation, and Dieckmann cyclization. Subsequent N-alkylation by the vinyl iodide 358 followed by Pd-catalyzed (enolate-driven)... 

The synthesis of 11-methoxymacroline 350 (239) required 6-methoxy-D-tryptophan 359, which was prepared by Larock s Pd-catalyzed heteroannulation of iodoaniline 360 and the propargyl compound 361 (prepared in turn from the Schollkopf chiral auxiliary derived from L-valine), followed by removal of the chiral auxiliary, and N(l)-methylation (Scheme 28). The 6-methoxy-D-tryptophan 359 was then transformed into the pentacyclic sarpagine derivative 362, via the 11-methoxytetracyclic ketone 354, following the same protocol as that employed in the A -methylsarpagine synthesis (vide... 

Fig. (3). Compartmentalization of the biosynthetic pathway of terpenoid indole alkaloids in plant cells. G10H geraniol 16-hydroxylase SLS secologanin synthase TDC tryptophan decarboxylase STR strictosidine synthase SGD strictosidine P-D-glucosidade T16H tabersonine 16-hydroxylase OMT S-adenosyl - L-methionine 16-hydroxytabereonine - 16-O-methyltransferase NMT S-adenosyl - /.-methionine 16-methoxy - 2,3-dihydro-3-hydroxytabersonine - A -methyltransferase D4H desacetoxy vindoline 4-hydroxylase DAT acetylcoenzyme A 4-O-deacetylvindoline 4-O-aeetyltransferase PRX peroxidase.

L-Tryptophan derivatives Serotonin, 5-methoxy-tryptamine (D 21.1) Vertebrates and invertebrates... 

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