Semicarbazones from N-hydroxyureas and amines: a novel entry in the reactivity of the acyl nitroso group.

The condensation of carbamoyl nitroso compounds, obtained by oxidation of N-hydroxyureas, with amines unexpectedly afforded semicarbazones (aka carbamoyl hydrazones). Although the substitution of the nitrosyl moiety might compete to afford the corresponding urea, an excess of amine led to the semicarbazone as the major product, which is presumably formed via isomerization of an initially generated acyl azo compound.

Different reactivity of hydroxylamine with carbamoyl azides and carbamoyl cyanides: synthesis of hydroxyureas and carbamoyl amidoximes.

The carbamoylating agents carbamoyl azides and carbamoyl cyanides (aka cyanoformamides) react with hydroxylamine in different ways, leading in the first case to N-hydroxyureas and, in the case of carbamoyl cyanides, to carbamoyl amidoxime derivatives. The synthetic procedure developed for the latter type of compound, which represents an interesting precursor for heterocyclic structures, allowed the highly efficient preparation of a wide selection of examples. The Z configuration of the double bond in the amidoxime moiety was proposed on the basis of comparison between experimental and calculated (13)C and (15)N NMR chemical shift values for the isopropyl and benzyl derivatives.

Concise total synthesis and structural revision of (+)-pestalazine B.

A convergent synthesis of the proposed structure of (+)-pestalazine B has been achieved in 4 steps using the N-alkylation of an unprotected tryptophan diketopiperazine with a 3a-bromopyrrolidinoindoline as the key step. Although its structure was confirmed by X-ray analysis, the spectroscopic data did not match those of the natural product. The versatility of the methodology allowed the preparation of several diastereomers, and the database generated led to the proposal of an isomeric structure for the natural alkaloid where the d-leucine and d-phenylalanine residues exchanged positions, which was corroborated by total synthesis.

Carbon dioxide as a carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas: scope and limitations.

Carbon dioxide can be used as a convenient carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas. The transient carbamate anion generated by treating a primary or secondary amine group in basic media can be activated with phosphorylating agents such as Diphenylphosphoryl azide (DPPA) and Diphenyl chlorophosphate (DPPCl) but also with other types of electrophiles such as SOCl(2), TsCl, or AcCl. The intramolecular trapping of the activated carbamate by a hydroxyl group leads to the formation of 2-oxazolidinones or 2-oxazinones in good to excellent yields.

Stereocontrolled and versatile total synthesis of bispyrrolidinoindoline diketopiperazine alkaloids: structural revision of the fungal isolate (+)-asperdimin.

Homo- and heterodimeric bispyrrolidinoindoline diketopiperazine alkaloids have been synthesized following a concise, versatile, and stereoselective route. Highlights of the sequence are a diastereoselective construction of the C3a-bromo-hexahydropyrrolo[2,3-b]indole nucleus, its Co(I)-induced C3a-C3a' dimerization, and the twofold or sequential amide-bond formation before cyclization to the diketopiperazine of the homo- or heterodimeric alkaloids, respectively. Stereochemical diversity is achieved through the choice of the appropriate amino acids combined with the base-induced epimerization of the C2-acyl-hexahydropyrrolo[2,3-b]indole at C2.

Expedient total syntheses of WIN 64745 and WIN 64821.

Bispyrrolidinoindoline diketopiperazine alkaloids were synthesized from a common intermediate in seven steps from commercially available amino acids. This versatile synthetic strategy has led to the accomplishment of the first total synthesis of heterodimeric WIN 64745 and a novel approach to homodimeric WIN 64821.

Mechanistic insights into the stereocontrolled synthesis of hexahydropyrrolo[2,3-b]indoles by electrophilic activation of tryptophan derivatives.

A three-step mechanism involving the formation and rearrangement of an intermediate with indoline-azetidine spirocyclic core structure was shown by DFT computations to account for the electrophilic cyclization of tryptophan derivatives to hexahydropyrrolo[2,3-b]indoles. The corresponding 3a-bromo derivatives have been obtained in high yields and synthetically useful exo/endo ratios.

Bispyridinium dienes: histone deacetylase inhibitors with selective activities.

A novel synthetic route to the cyclostellettamines 1 using as the key step a microwave-mediated macrocyclic ring-closing metathesis of precursors bispyridinium dienes 10 followed by catalytic hydrogenation has been developed. The open-chain bispyridinium dienes 10 showed uniformly higher histone deacetylase (HDAC) inhibitory potency than the natural products. Diene 10b inhibited HDAC1 and was inactive on HDAC4, whereas 10a showed a weak inhibition of HDAC1 and a higher activity on HDAC4.