Marta Figueredo

A Metal-Free General Procedure for Oxidation of Secondary Amines to Nitrones

An efficient and metal-free protocol for direct oxidation of secondary amines to nitrones has been developed, using Oxone in a biphasic basic medium as the sole oxidant. The method is general and tolerant with other functional groups or existing stereogenic centers, providing rapid access to enantiomerically pure compounds in good yields.

Efficient synthesis of α,β-unsaturated γ-lactones linked to sugars

Abstract A series of structurally diverse unsaturated sugar-derived lactones has been prepared. α,β-Butenolides were introduced to the sugar moiety starting from epoxides, while α-methylene-γ-lactones were constructed from a carbonyl precursor, either an aldehyde, a ketone or a lactone. In the last case, an unprecedented Reformatsky-type reaction has been developed.

Enantioselective Approach to Securinega Alkaloids. Total Synthesis of Securinine and (−)-Norsecurinine

The most representative securinega alkaloids have been synthesized through a new strategy involving the palladium-catalyzed enantioselective allylation of a cyclic imide, a vinylogous Mannich reaction, and a ring-closing metathesis process, as the key steps. The diastereoselectivity of the vinylogous Mannich reaction was in partial agreement with DFT theoretical calculations performed in a model system. The synthesis of (-)-norsecurine has been accomplished in nine steps from succinimide and 14% overall yield and that of securinine in 10 steps from glutarimide and 20% overall yield. Both syntheses compare favorably with those previously described. The three key transformations have been performed in a synthetically useful scale (more than 500 mg). Moreover, since the enantioselectivity was originated by a chiral phosphine ligand, the antipode of which is readily available, the same route is expected to give access to (+)-norsecurinine and virosecurinine.

Diastereoselective synthesis of allosecurinine and viroallosecurinine from menisdaurilide.

A new and versatile synthetic route to Securinega alkaloids is reported. The first synthesis of allosecurinine has been accomplished in seven steps and 40% yield, starting from (+)-menisdaurilide, using a vinylogous Mannich reaction as the key transformation. Similarly, viroallosecurinine has been synthesized from (-)-menisdaurilide.

Efficient synthesis of (S)-3,4-dihydro-2-pivaloyloxymethyl-2H-pyrrole 1-oxide

Abstract A convenient synthesis of the title nitrone is reported. The sequence starts from ethyl l -pyroglutamate as the source of chirality and the key step is the generation of an unstable α-methoxy- N -carboxylate ion, which readily decomposes to an imine. The oxidation of the imine with methyl(trifluoromethyl)dioxirane provides the enantiopure nitrone, which is trapped with dimethyl acetylenedicarboxylate.

1,3-Dipolar cycloadditions of 3,4,5,6-tetrahydropyridine 1-oxide to α,β-unsaturated lactones : stereochemical assignment and conformational analysis of the products

Abstract We have investigated the 1,3-dipolar cycloaddition of nitrone 1 to seven, six, and five membered α,β-unsaturated lactones ( 2 , 3 , and 4–6 ) and 2,5-dihydrofuran, 18 . In all these reactions, exo adducts are obtained as major or exclusive products. To elucidate the stereochemistry of the obtained heterocyclic compounds, an accurate conformational analysis has been performed. Important differences in their conformational behavior in solution have been found as a function of the lactone ring size and the presence or absence of a carbonyl group. This study points out the existence of an attractive interaction between the nitrogen lone electron pair and a carbonyl group at a fitting distance, which induces the preference for the cis fusion of type E in the furanonic exo adducts ( 10 , 12 , 13 , 15 , and 16 ). In all the other cases, where this distance is too long ( 7 , 8 , 9 , 11 , 14 ) or no carbonyl group is present in the molecule ( 20 ), the trans invertomers predominate.

Synthesis and 1,3-dipolar cycloadditions of a new enantiopure cyclic nitrone

Abstract A new enantiopure cyclic nitrone has been efficiently synthesized from a d -glyceraldehyde derivative. Its 1,3-dipolar cycloaddition to different classes of dipolarophiles show complete antifacial selectivity, furnishing highly functionalized enantiopure bicyclic isoxazolidines.

Cycloaddition reactions of 3,4-dihydro-2H-pyrrole 1-oxide with α,β-unsaturated lactones

Abstract The cycloadditions of nitrone 2 to α,β-unsaturated lactones 3–6 have been studied under several reaction conditions. The adducts derived from pentenolide 5 and hexenolide 6 are the first examples of the pyrano[3,4- d ]pyrrolo[1,2- b ]isoxazole and oxepino[3,4- d ]pyrrolo[1,2- b ]isoxazole systems respectively. The stereochemistry of the products has been established using high field nmr techniques. In all cases the major cycloadduct derives from an exo orientation of the transition state.

ONE STEP PREPARATION AND 1,3-DIPOLAR CYCLOADDITIONS OF (S)-5-HYDROXYMETHYL-1-PYRROLINE N-OXIDE

Abstract The cyclic nitrone 1b has been prepared in enantiomerically pure form by direct oxidation of L-(+)-prolinol with dimethyldioxirane. A complete diastereoface differentiation has been observed in the 1,3-dipolar cycloaddition reaction of this nitrone to several 1,2-disubstituted electron deficient olefins.

Synthesis of Purine Nucleosides Built on a 3-Oxabicyclo[3.2.0]heptane Scaffold

The photochemical [2 + 2] cycloaddition of chiral 3-chloro and 3-fluoro-5-hydroxymethyl-2(5H)-furanone to ethylene and acetylene has been studied. The effect of the halogen atom on the chemical yield and facial diastereoselectivity of the cycloaddition process has been evaluated. From the major anti cycloadducts, practical syntheses of several purine cyclobutane and cyclobutene-fused nucleosides containing a halogen atom have been developed. The anti-HIV activity of the new nucleoside analogues has been evaluated.