A concise route to the right wing of ciguatoxin

A concise route to the HIJKLM-ring fragment 10 of ciguatoxin (CTX) and 51-hydroxyCTX3C was developed in which oxiranyl anion addition and intramolecular carbonyl olefination were utilized as key transformations. The present procedure requires only 23 steps from the I-ring 5, while 35 steps were employed in a previous synthesis of the corresponding right wing 11 of CTX3C. The high efficiency of the present synthesis ensures a supply of 10 for total synthesis and biomedical applications.     

An efficient and facile multicomponent synthesis of 4,6-diarylpyridine derivatives under solvent-free conditions

We present an efficient and facile synthesis of 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles (5a–j) via a four-component system of aromatic aldehydes (1), acetophenones (2), ethyl cyanoacetate (3), and ammonium acetate (4). The short reaction time coupled with the simplicity of the reaction procedure and clean reaction make this method one of the most efficient methods for synthesis of this class of compounds.     

Stereoselective synthesis of enantiopure analogues of (−)-cephalotaxine

The asymmetric total synthesis of three analogues of (?)-cephalotaxine with structural modification of the aromatic ring was achieved in 16 steps and acceptable overall yields. The procedure used was quite similar to that reported by our group for the total synthesis of (?)-cephalotaxine in 2004. The enantiopure spiranic compound 4 is a common intermediate on which various aromatic groups can be introduced. Unexpected and interesting different chemical behaviors were observed during these syntheses.     

Stereo- and regioselective formation of silyl enol ethers via oxidation of vinyl anions

Oxidation of E- and Z-vinyl lithiums with silyl peroxides 5 affords silyl enol ethers 3 in good to excellent yield with retention of configuration. This methodology represents a useful new procedure for the stereo- and regioselective synthesis of ketone enolates.     

A highly stereoselective and efficient synthesis of enantiomerically pure sitagliptin

A highly stereoselective and efficient synthesis of sitagliptin 1 consisting of a chiral β-amino acid unit has been achieved through 6 steps from commercially available 2,4,5-trifluorobenzaldehyde 4. The chiral antidiabetic drug was obtained with almost perfect enantiomeric purity (>99.9% ee) in 40.9% overall yield. The key feature of the synthesis is the addition of a malonate enolate to a chiral sulfinylimine in more than 99:1 dr. Our synthetic procedure proved to be highly efficient, economical, and sustainable.     

New phosphorylating reagents for deoxyribonucleosides and oligonucleotides

New phosphorylating reagents 1 and 2 were prepared in three steps from 4-hydroxybenzaldehyde. They showed good efficiency in the solid phase synthesis of 5′-phosphate monoester nucleosides. End-phosphate DNA sequence synthesis demonstrated the efficiency of the new reagents (1 and 2) according to the general procedure of automated DNA synthesis. The oxidation of P(III) to P(V) and the removal of benzyl protecting groups were achieved in a single step by treatment with a 0.02 M I₂/pyridine/H₂O solution. Due to this one-pot treatment, it is possible to use the phosphorylating reagents (1 and 2) for the synthesis of base-sensitive ODNs. The reagents 1 and 2 are unique among phosphorylating reagents.     

Epoxide synthesis in the butadiene-iron tricarbonyl series

The synthesis of functionalized epoxide-alcohols 8 to 11 is reported. The Sharpless procedure [TBHP- VO(acac)₂] is fully compatible with the presence of an organoiron complex.     

Stereo-controlled synthesis of polypropionate ester derivatives using titanium complexes

A method for the stereocontrolled synthesis of polypropionate ester derivatives by means of titanium complexes is described. The general procedure involves an allyltitanium complex which allows the formation of an enolsilane bearing two stereocentres and an alkoxy titanium complex used in a tandem aldol–Tischtschenko reaction. These two steps are very highly diastereoselective. We present here the study of the tandem aldol–Tischtschenko reaction involving enolsilanes possessing different steric hindrance. © 2000 Académie des sciences / Éditions scientifiques et médicales Elsevier SAStitanium complexes / aldol reaction / Tischtschenko reaction / asymmetric induction     

One-pot synthesis of heterocyclic compounds initiated by chemoselective addition to β-acyl substituted unsaturated aldehydes with nucleophilic tin complexes

β-Acyl substituted unsaturated aldehydes 1 were revealed to be good precursors for the synthesis of various heterocyclic compounds by the combination with tin nucleophiles. Various 2-monosubstituted pyrroles were prepared in an one-pot procedure via the reductive amination of formyl groups of 1 by using Bu₂SnIH–HMPA complex. One-pot synthesis of heterocycles was carried out initiated by chemoselective reduction of 1 with Bu₃SnH–HMPA complex and the subsequent reaction with heterocumulenes. Furthermore, the one-pot synthesis of nitrogen heterocyclic compounds accompanying chemo-, regio- and diastereoselective carbon–carbon bond formation in side chain moieties was effectively accomplished initiated by the regio- and diastereoselective allylation of the formyl group of 1 with allylic tin species.     

A stereospecific total synthesis of aklavinone

A stereospecific synthesis of aklavinone (2) in 16 steps from 5-methoxy- 1-tetralone with an overall yield of 6.5% is described. Regiospecific control in forming the BCD-ring chromophore was accomplished by coupling of a preformed bicyclic AB-ring aldehyde (29) with a nucleophilic D-ring carboxamide (3), with stepwise bond formation as illustrated in equation 2. The coupled product was subsequently transformed into (±)-aklavinone. An enantioselective synthesis of aklavinone was achieved in 53%. e.e. using the procedure of Sharpless for the asymmetric epoxidation of allylic alcohol 24¹³     

Synthesis of JOSIPHOS-type ligands via a diastereoselective three-component reaction and their application in asymmetric rhodium-catalyzed hydroborations

The recently reported diastereoselective three-component reaction for the synthesis of chiral propargylamines was used for a new stereoselective synthesis of JOSIPHOS-type ligands 2a–d. The present synthesis gives the desired diphosphines in good yields without the need of resolution. Ligands 2a–d were applied to the rhodium-catalyzed hydroboration of styrene.     

Procyanidin oligomers. A new method for 4→8 interflavan bond formation using C8-boronic acids and iterative oligomer synthesis through a boron-protection strategy

Interest in the synthesis of procyanidin (catechin or epicatechin) oligomers that contain the 4→8 interflavan linkage remains high, principally due to research into their health effects. A novel coupling utilising a C8-boronic acid as a directing group was developed in the synthesis of natural procyanidin B3 (i.e., 3,4-trans-(+)-catechin-4α→8-(+)-catechin dimer). The key interflavan bond was forged using a novel Lewis acid-promoted coupling of C4-ether 6 with C8-boronic acid 16 to provide the α-linked dimer with high diastereoselectivity. Through the use of a boron protecting group, the new coupling procedure was extended to the synthesis of a protected procyanidin trimer analogous to natural procyanidin C2.     

Microwave-assisted synthesis of fused pyrazolo[3,4-b]pyrazines by the reaction of ortho-aminonitrosopyrazoles and cyclic β-diketones

Novel fused pyrazolo[3,4-b]pyrazines 3 were prepared by assisted microwave cyclocondensation reaction of ortho-aminonitrosopyrazoles 1 and cyclic β-diketones 2 in dimethylformamide. This protocol provides a simple procedure for the synthesis of the title compounds with the advantages of easy work-up, mild reaction conditions and good yields.     

Synthesis of α-alkoxyalkyltributyllead compounds via the reaction of tributylplumbyllithium with α-chloroethers,and the conjugate addition of tributylplumbyllithium to enones

α-Alkoxyalkyltributylleads 1 were prepared from the reaction of tributylplumbyllithium with α-chloroethers 2. This procedure is more convenient than the conventional method which involves transmetallation from the corresponding α-alkoxyalkyltrialkyltin. Tributylplumbyllithium was also used for the synthesis of β-oxo-organolead 4.     

Efficient synthesis of [H2]-tetrahydrodicranenone B and a 3-oxa-analogue resistant against β-oxidation

A short efficient synthesis of two analogues of tetrahydrodicranenone B as well as a formal synthesis of tetrahydrodicranenone B (1) itself has been devised. The approach is based on an addition/elimination sequence of in situ prepared organocuprates to the iodocyclopentenone (9). The procedure is compatible with functionalised substituents.     

A total synthesis of corydaline

A total synthesis of (±)-corydaline 1 is described in which the condensation of 3,4-dihydro-6,7-dimethoxyisoquinoline 10 with 3,4-dimethoxyhomophthalic anhydride 9 is utilized as the convergent step. A new procedure for the preparation of 9 is also described. The Beckmann rearrangement of an α-ketooxime 4 with phosphorus pentachloride in chloroform is shown to afford the 3-chloro-1-(2H)isoquinolone 5 by a fragmentation-recombination type mechanism.     

Stereoselective synthesis of a new chiral synthon: a cyclic pseudodipeptide containing an aspartic acid derivative and l-valine

A simple stereoselective synthesis of cyclic synthons 4a,b and 10a,b, derived from an l-valine unit and an unnatural derivative of the aspartic acid, has been accomplished starting from the chiral synthon 1 and following the procedure already reported by us for the synthesis of similar compounds. These cyclic synthons are interesting substrates because they can behave as both electrophiles and nucleophiles and could be useful starting materials for the preparation of higher peptides such as, for instance, the unnatural tetrapeptides 15 and 18, through the condensation of 4a with 6a or 13 with 17, respectively.     

Stereoselective synthesis of l-isonucleosides

l-Isonucleosides 17 and 19 were stereoselectively synthesised from (S)-glycidol by two different procedures. The key step was the synthesis of a chiral dihydrofuran which was carried out by oxidation/elimination of 8 and by ring-closing metathesis of diene 10. The procedure can be applied to the synthesis of both enantiomers.     

A route to enantiomerically pure 5-(2′-hydroxyethyl)cyclopent-2-en-1-ol and its absolute configuration by Mosher esters

The (±)-5-(2′-hydroxyethyl)cyclopent-2-en-1-ol 1 was prepared in a one-pot procedure, and was resolved using lipase AK and vinyl acetate with high ee. This provides a readily available chiral synthon for the synthesis of a wide variety of biologically interesting molecules. Further, the absolute configuration of diol 1 was confirmed directly by the Mosher ester method.     

Expeditious synthesis of TADDOL-derived phosphoramidite and phosphonite ligands

A simple and reliable protocol for the synthesis of TADDOL-derived monodentate ligands is reported. The reaction of the requisite TADDOL with PCl₃ is immediately followed by the treatment of the crude intermediate with both nitrogen and carbon nucleophiles. Several previously unknown or difficult-to-make phosphoramidite and phosphonite ligands L1–L3 and L4–L9 were accessed using this novel procedure.