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Novel reactions under Pictet-Spengler conditions between tryptophan methyl ester/tryptamine and 2-oxoaldehydes have been developed and successfully utilized for the total synthesis of Merinacarboline (A and B), Eudistomin Y1, Pityriacitrin B, Pityriacitrin, Fascaplysin and analogues.2-Oxoaldehydes (OA) are among a few precursors that have been used extensively to synthesize a large variety of heterocyclic compounds. 1 Pictet-Spengler is one of the various reactions reported on OA leading to the synthesis of b-carbolines. 2-11 A large number of naturally occurring b-carbolines with acyl substitution at the C-1 position have shown promising antiinammatory, 2 anti-malarial, 12 anti-cancer, 3,13 anti-phospholipase A2, 14 anti-microbial, 15 and anti-bacterial activities. 16 In view of these biochemical observations, convenient synthetic methods for the synthesis of such constructs are desirable. Even though the Pictet-Spengler reaction of tryptamine/tryptophan/ tryptophan methyl ester with OA for generation of 1-substituted b-carbolines has been explored, 2,6 a few areas are still untouched. As we know in contemporary organic synthesis, coupled domino reactions, wherein two or more domino processes occur sequentially in the same reaction, are considered to be most effective for the synthesis of complex organic compounds using simple and readily available building blocks. 17,18 In this context, we developed a few unexplored reactions between tryptophan methyl ester/tryptamine and 2-oxoaldehydes with a focus on establishing a multicoupled domino strategy for the synthesis of various marine based natural products and their analogues.We initiated the present study with a reaction of 2,4-dimethoxy acetophenone 1 with tryptophan methyl ester 2 in the presence of iodine in DMSO. The reaction of 1 (1 equiv.) and 2 (1 equiv.) with I 2 (1 equiv.) in DMSO at 90 C for 1.5 h afford the desired product in low yield (38%, Table 1, entry 15). To improve upon the yields of desired product, a preliminary set of reactions between tryptophan methyl ester (1 equiv.) and acetophenone (1 equiv.) under different condition were carried out (Table 1). Table 1 Optimization studies for synthesis of 3a employing 2,4-dimethoxy acetophenone as building block a Entry (Equiv.) Temp. Time Yield b (%)

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An efficient one-pot four-component domino protocol for the combinatorial synthesis of novel 1,4-dihydropyrano[2,3-c]pyrazol-6-amines has been achieved. This transformation presumably occurs via cyclization-Knoevenagel condensation-Michael addition-tautomerism-intramolecular O-cyclization-elimination sequence of reactions. The significant features of this reaction include expedient one-pot process, short reaction time, no column chromatographic purification, excellent yield, and readily available starting materials.

Novel amino acid substituted imidazoles engendered from amino acid alkyl ester hydrochlorides and 2-oxoaldehydes as a result of selenium dioxide promoted unconventional reaction in a basic environment is presented for the first time. Despite the nature of the 2-oxoaldehydes/amino acids used, the imidazoles generated had a functional core structure, and all of the reactions meticulously retained regioselectivity. The imperative feature of these reactions was the uniqueness of selenium dioxide in fixing two nitrogen atoms from amino acids through an in situ generated ArCOCHN1N2 system.

Our interest in generating amide bonds by employing the activated C=N system has led to the development of an efficient oxidative amidation reaction between 2‐oxoaldehyde and weak nucleophilic amines (anilines, benzamides and sulfonamides). Mechanistic studies support the involvement of α‐carbonylimine (–CO–C=N–) based compounds or intermediates as a central feature of the reaction, in which an adjacent CO moiety enhances the electrophilicity of the C=N system, which favors attack of the oxidant (TBHP or SeO2), thereby resulting in the generation of the desired products in good yields. The direct oxidative coupling of 2‐oxoaldehydes and weak nucleophilic amines has been accomplished through either MgSO4–TBHP–pyridine/CuBr, or SeO2·pyridine promoted methods. In the current study, SeO2·pyridine emerged as a versatile reagent with which to promote initial α‐carbonylimine formation between 2‐oxoaldehyde and weak nucleophilic amine, and subsequent oxidation to the corresponding α‐carbonylamide. The reported methodology constitutes one of the few reports of the synthesis of α‐ketoamides from anilines, perhaps the second report for the generation of α‐ketoimides, and the first report of the generation of 2‐oxoamides with sulfonamides.

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