A series of racemic dipodazine analogues 9 were prepared in 22 -80% yield from (3Z,6RS)-3-[(dimethylamino)methylidene]-6-methyl-1-(phenylmethyl)piperazine-2,5-dione (7) (Scheme 1), which was prepared in four steps from (RS)-alanine methyl ester hydrochloride. The preparation of nonracemic 7 from (S)-alanine methyl ester hydrochloride failed, since the introduction of the enamino functionality at position 3 of the precursor 6 was accompanied by almost complete racemization.Introduction. -Many marine natural products with potent pharmacological activities contain an indole nucleus [1]. Such indole derivatives are, e.g., aplysinopsins (1; Fig. 1), which have attracted considerable interest due to their cytotoxicity towards cancer cells and their ability to affect neurotransmitters [2]. Recently, the nortopsentins and meridianins (2), another series of indole alkaloids with interesting antitumor properties, have been isolated from the sponge Spongosorites ruetzleri, and from tunicate Aplidium meridianum [3]. Structurally, the meridianins comprise a brominated and/ or hydroxylated indole nucleus bearing a 2-aminopyrimidine substituent at the 3-position [4], and they are potent inhibitors of several protein kinases [5]. Other interesting biologically active indole alkaloids are 1) tryptophan-dehydrobutyrine diketopiperazine (TDD; 3) [6], a fungal metabolite isolated from Streptomyces spectabilis and Streptomyces sp. M1513-bF5; 2) barettin (4) [7], isolated from the marine sponge Geodia barretti, a diketopiperazine condensation product of 6-bromodehydrotryptophan and arginine; as well as 3) dipodazine (5) [8], a diketopiperazine derivative composed of dehydrotryptophan and glycine, which has been isolated from Penicillium dipodomyis and meat-associated P. nalgiovese. The syntheses of compounds 3 -5 and their analogues include condensation of 1H-indole-3-carbaldehyde with piperazine-2,5-dione derivatives as the key-step [6 -8].Alkyl 3-(dimethylamino)propenoates and related enaminones have been recently used as building blocks for the preparation of dehydro-alanine derivatives and many heterocyclic systems such as fused pyridines, pyrimidines, pyranones, and other compounds, including some natural products (e.g., indole alkaloids) and their synthetic analogues [9]. Various chiral analogues of 3-(dimethylamino)propenoates have also been prepared from commercially available, enantiomerically pure starting materials such as a-amino acids and (+)-camphor, and were employed as key intermediates and reagents in the synthesis of 1) functionalized heterocycles, e.g., 3-heteroarylalanine derivatives and related compounds, 2) heterocyclic analogues of dipeptides, and 3) terpene-func-
