Synthesis of D-D4FC, a biologically active nucleoside via an unprecedented palladium mediated Ferrier rearrangement-type glycosidation with an aromatization prone xylo-furanoid glycal

D-D4FC (1) is an anti-HIV agent currently under phase II clinical trial (Pharmaset Inc). Its molecular architecture is suitable for a Ferrier rearrangement kind of operation on a furanoid glycal to fix the position of the double bond and the relative stereochemistry. Despite the fact that classical Ferrier rearrangement does not work on furanoid glycals, a palladium mediated modified protocol has been developed for the glycosidation of an aromatization prone xylo-furanoid glycal (5) for the synthesis of D-D4FC.     

Total synthesis of amiclenomycin, an inhibitor of biotin biosynthesis

We describe the first synthesis of amiclenomycin, a natural product that has been found to inhibit biotin biosynthesis and, as a consequence, to exhibit antibiotic properties. Structure 1, with a trans relationship between the ring substituents. had previously been proposed for amiclenomycin on the basis of its 1H NMR spectrum. We have prepared the trans and cis isomers 1 and 2 by unequivocal routes and we conclude that the natural product is in fact the cis isomer 2. The properly substituted cyclohexadienyl rings were constructed first. A cycloaddition reaction between 1,2-di(phenylsulfonyl)ethylene and the N-allyloxycarbonyl diene 13, followed by reductive elimination of the phenylsulfinyl groups, gave the cis isomer 15. To obtain the trans isomer, the O-trimethylsilyl diene was used to give the cis hydroxylated Diels-Alder adduct 33, which was transformed into the corresponding trans amino derivative by means of a Mitsunobu reaction. The L-alpha-amino acid functionality was introduced by means of a Strecker reaction on the aldehydes 16 and 42, followed by enzymatic hydrolysis with immobilised pronase.     

Stereoselective synthesis of Sch 642305, an inhibitor of bacterial DNA primase

Sch 642305 is a fungal nonanolide, which inhibits bacterial DNA primase and HIV-1 Tat transactivation. The enantioselective synthesis of Sch 642305 was succeeded starting from useful chiral building block via stereoselective dianion alkylation of β-ketosulfoxide and lactonization.     

Stereoselective synthesis of triterpene and steroid 2-deoxy-α-glycosides using iodonium dicollidine perchlorate

2-Deoxy-α-glycosides of oleonane type triterpene alcohols and deoxycholic acid were synthesized by glycosylation with glycal acetates in the presence of iodonium dicollidine perchlorate followed by deiodination and deprotection. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 601–605, March, 1997.     

Stereoselective synthesis of MLN4924, an inhibitor of NEDD8-activating enzyme

MLN4924 (1), which is in clinical trials as an anticancer agent, was stereoselectively synthesized from d-ribose via a route involving stereoselective reduction, regioselective cleavage of an isopropylidene moiety, and selective displacement of a cyclic sulfate moiety as key steps.     

Stereoselective synthesis of the α-glucosidase inhibitor nectrisine

The α-glucosidase inhibitor nectrisine was synthesised in 12 steps (31% overall yield) starting from d-serine. The three contiguous stereocentres of this iminosugar were introduced via a highly diastereoselective boron mediated glycolate aldol reaction.     

Stereoselective formal synthesis of the potent proteasome inhibitor: salinosporamide A

(2R,3S)-α-Methylenelactam 3, the key intermediate in Corey’s syntheses of salinosporamide A, has been synthesized from (S)-methyl 2-hydroxymethylpyroglutamate through chemoselective O-protection, regio- and stereoselective N-methylnitrone cycloaddition and quaternarization-elimination reactions as the main steps.     

Efficient synthesis of β‐(1,6)‐linked oligosaccharides through microwave‐assisted glycosylation

A microwave‐assisted glycosylation method was developed for efficient synthesis of oligosaccharides. Di‐functional AB monomers, 2,3,4‐tri‐O‐acetyl‐α‐d ‐galactopyranosyl bromide ( 3a ) and 2,3,4‐tri‐O‐acetyl‐α‐d ‐glucopyranosyl bromide ( 3b ) were designed and synthesized as weakly reactive monomers to avoid unwanted glycosylation or degradation during preparation and storage. The glycosylations of these monomers gave low conversions and low molecular weight oligosaccharides at rt, reflux, and under low microwave energy irradiation. However, the glycosylation became very effective when high microwave energy was applied, giving 100% conversion and producing oligosaccharides with M_n = 4.76 kDa for 3a and M_n = 4.05 kDa for 3b. The acetylated oligosaccharides were further subjected to deprotection for structural analysis, which indicated the oligosaccharides contain predominantly linear β‐(1,6)‐glycosyl linkages. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3693–3699     

Stereoselective synthesis of the glycosidase inhibitor australine through a one-pot, double-cyclization strategy

[reaction: see text] A stereocontrolled, convergent synthesis of the alkaloid australine, a glycosidase inhibitor of the pyrrolizidine class, is described. The chiral starting materials were ketone 3, derived from L-erythrulose, and alpha-alkoxy aldehyde 4, prepared from L-malic acid. A key step of the synthesis was the highly stereoselective aldol reaction between 4 and a Z boron enolate derived from 3. Another key step was the one-pot construction of the bicyclic pyrrolizidine system by means of a three-step sequence of SN2 displacements induced by benzylamine on a trimesylate precursor.     

Carbohydrate-based oxepines: ring expanded glycals for the synthesis of septanose saccharides

A ring-closing metathesis (RCM) approach to a family of carbohydrate-based oxepines is described. A variety of readily accessible, protected monosaccharide derived dienes were used to demonstrate the utility of the synthetic sequence and to investigate how factors such as rigidification and deoxygenation mediate RCM using the Grubbs or Schrock catalyst. The seven-membered cyclic enol ethers are ring expanded glycals to be used in the synthesis of septanose carbohydrates.     

Stereoselective synthesis of an advanced taxusin intermediate: an application of the type 2 intramolecular Diels–Alder reaction

Stereoselective synthesis of an advanced taxusin intermediate is described. The key step is the successful application of the type 2 intramolecular Diels–Alder (IMDA) reaction for the assembly of the tricyclic core of this natural product.     

Efficient and direct synthesis of saccharidic 1,2-ethylidenes, orthoesters, and glycals from peracetylated sugars via the in situ generation of glycosyl iodides with I2/Et3SiH

Peracetylated sugars can be efficiently converted into the corresponding 1,2-ethylidenes, -orthoesters, and -glycals via the in situ generation of glycosyl iodides promoted by I₂/Et₃SiH. The approach is straightforward and avoids isolation of the sensitive iodinated intermediates.     

First synthesis of 2'-deoxyfluoropuromycin analogues: experimental insight into the mechanism of the Staudinger reaction

The N(6),N(6)-dedimethyl-2'-deoxyfluoro analogue of puromycin (= 3'-deoxy-N(6),N(6)-dimethyl-3'-[O-methyltyrosylamido]adenosine), its 2',3'-regioisomer and a 3'-cytidyl-5'-(2'-deoxyfluoro)puromycyl dinucleotide analogue were synthesized following an approach involving i) the diastereospecific nitrite-assisted formation of a lyxo nucleosidic 2',3'-epoxide from an adenosine-2',3'-ditriflate derivative in a biphasic solvent mixture; ii) the regio- and stereoselective epoxide ring opening with sodium azide under mildly acidic aqueous conditions, iii) the stereospecific introduction of the fluor atom using DAST and iv) the reaction between the nucleosidyl or dinucleotidyl azide and an active ester of the N-protected amino acid using highly efficient solution conditions for the Staudinger-Vilarrasa coupling, to obtain the corresponding carboxamide directly from the in situ formed iminophosphorane. This coupling reaction furnished sterically quite demanding amides in 94 % isolated yields under very mild conditions and should therefore be of a more general value. Under certain reaction conditions we isolated (amino)acyltriazene derivatives from which dinitrogen was not eliminated. These secondary products are trapped and stabilized witnesses of the first intermediate of the Staudinger reaction, the phosphatriazenes (phosphazides, triazaphosphadienes) which usually eliminate dinitrogen in situ and rapidly rearrange into iminophosphoranes, unless they are derived from conjugated or sterically bulky azides and phosphines. The acyltriazenes could either be thermally decomposed or converted to the corresponding N-alkyl carboxamides through proton-assisted elimination of dinitrogen. All compounds were carefully characterized through MS spectrometry, (1)H, (19)F, (31)P and (13)C NMR spectroscopy.     

Efficient synthesis of isogranulatimide C, an analogue of the marine G2 checkpoint inhibitor alkaloid isogranulatimide

A three-step procedure to isogranulatimide C starting with the thermal condensation of 3-chloroindole with imidazole and proceeding in 41% yield is described.     

E -型α, β-不饱和酰胺的立体选择合成

本文报道了在钯及二丁基碲存在下, 溴代乙酰胺与醛的亲卤缩合反应, 提供了E型α, β-不饱和酰胺的立体选择合成。