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Financial support from the Brazilian agencies Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES-DGU Project number 200/09), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) is gratefully acknowledged. The Spanish Ministerio de Ciencia e Innovacion (MICINN) (project numbers PHB2008-0037-PC, CTQ2007-62771/BQU, CTQ2010-20387, Consolider INGENIO 2010 grant number CSD2007-00006), (FEDER), Generalitat Valenciana (project PROMETEO/2009/038), and the University of Alicante are also gratefully acknowledged.

Countercurrent chromatography (CCC) was employed as a useful, fast and economic alternative to conventional chromatography techniques for the purification of a synthetic pterocarpanquinone, LQB-118. The separation was performed in a two-step CCC with the solvent system hexane-chloroform-methanol-water 2:1.5:5:2 in both steps. Traditional purification of these reaction products by silica gel column chromatography demanded a large amount of solvent and time, besides allowing the irreversible adsorption of the compound in the column. The use of 1H NMR for the calculation of KD of target compound is proposed as an alternative for HPLC measurements.

(−)-Nebracetam 1 was stereoselectively prepared for the first time, allowing the determination of its absolute configuration as ( R ). The pivotal intermediate in the synthesis, 1-benzyl-4-[( S )-2,2-dimethyl-1,3-dioxolan-4-yl]-pyrrolidin-2-one 6 , was previously obtained in 60% yield and 90% ee from an enoate derived from d -mannitol. Two approaches were investigated to synthesize ( R )-(−)-nebracetam 1 and analogues 4 and 5 from 6 . Compound 6 was transformed into WEB-1868 2 . Mesylation of the hydroxyl group in 2 , followed by nucleophilic substitution with azide and reduction led to target 1 . Compounds 4 and 5 were synthesized by using morpholine and N -methyl piperazine as nucleophiles. Compounds 4 and 5 were also prepared, in higher yields and similar ee, through the reductive amination of aldehyde 10 , obtained in two steps from 6 .

The absolute configuration of three contiguous newly generated stereocenters in (1 R ,2 R ,3 S ,5 S ,1′ R )-3-(1′-(4-methoxyphenyl)ethyl)-6,6-dimethylbicyclo [3.1.1] heptan-2-ol (6), stereoselectively prepared from β-pinene in four steps, was established on the basis of 1 H NMR data and molecular modeling.

The oxidative cleavage of D‐(+)‐mannitol‐diacetonide with sodium periodate lead to a mixture of D‐(+)‐glyceraldehyde, its hydrate and oligomeric derivatives. In spite of the low concentration of free glyceraldehyde (estimated in ∼20%, by NMR), good yields were obtained in nucleophilic additions involving this mixture and a variety of nucleophiles (amines, phosphonates, phosphoranes, nitronates, organometallic compounds).

A two-step route to 5-carbapterocarpens, hydroxylated at different positions, is presented from tetralones and aryl bromides in good overall yields.

Scheme 1-Preparation of α-aryl-tetralones Under these conditions the α-aryltetralones 5 were obtained from good to high yields. The next step was the conversion of 5 into the 5deoxypterocarperns through the one-pot demethylation-cyclization catalyzed by BBr3 (Scheme 2). The products were obtained in high yields, without needing any process of purification. In the case of 5c-d the demethylation was chemoselective, and methoxy derivatives 7a-b were obtained only by keeping the reaction at 0 oC.

The α-arylations studied are shown in Scheme 1, Table 1. We start our study with the reaction between 1a by 2a and a clean transformation of 2a was observed under microwave irradiation, leading to 3a (entry 1). The α-arylation goes very well even for more sterically hindered ortho-bromophenols 2b and 2c (entries 2 and 3). The same trend was observed in the reactions between 1b and 2a-c (entries 4-6). We also used the oxime-derived palladacycle precatalyst 5, synthesized by the Spanish group and previously used in several carbon-carbon bondforming reactions in organic solvents as well as in neat water or aqueous solvents. 2 As shown in entry 7, a complete conversion was also observed in this case. In contrast with the reported procedures under thermal conditions, which requires more than 2h to completion, under microwave irradiation a total conversion of O-protected ortho-bromophenols was achieved after 1h of reaction. In addition, products of α,α-diarylation, which are side products in these reactions, could not be detected in the crude product. The chemical yield of these reactions will be reported soon.

The oxidative cleavage of D‐(+)‐mannitol‐diacetonide with sodium periodate lead to a mixture of D‐(+)‐glyceraldehyde, its hydrate and oligomeric derivatives. In spite of the low concentration of free glyceraldehyde (estimated in ∼20%, by NMR), good yields were obtained in nucleophilic additions involving this mixture and a variety of nucleophiles (amines, phosphonates, phosphoranes, nitronates, organometallic compounds).

Chiral pyrrolidin-2-ones have been prepared through the reductive cyclisation of γ-nitro-esters. These intermediates were obtained by syn -stereoselective conjugate addition of nitronates to a Z -enoate derived from d -(+)-mannitol. This route was used to prepare the cognitive enhancer ( S )-WEB-1868.