The preparation of 2-iodoamides from glucals and their further transformations into oxazolines

2-Deoxy-2-iodo-glycosylamides have been prepared from a variety of protected d-glucals by their reaction with N-iodosuccinimide and amides. Benzyl protected 2-iodoamides, when treated with sodium hydride and 15-crown-5, gave stable C1 N-linked 2-glycooxazolines as the major products. Silyl protected 2-iodoamides afforded the C1 O-linked 2-glycooxazolines; presumably by the rearrangement of unstable N-acylaziridine intermediates.     

Protection of Ag Clusters by Metal-Oxo Modules

Monodisperse and atomically precise Ag nanoclusters have attracted considerable recent research interest. A conventional silver cluster usually consists of a silver metallic kernel and an organic peripheral ligand shell. Nevertheless, the present inevitable problem is the unsatisfied stability of such nanoclusters. In this concept, we will give an introduction to Ag clusters protected by metal-oxo modules, which exhibit enhanced stability and unique properties. Accordingly, three different types of clusters are summarized: (1) Ag clusters protected by mononuclear oxometallates; (2) Ag clusters protected by block-like metal-oxo clusters; (3) Ag clusters protected by hollow-like metal-oxo clusters. The aim of this concept is to offer possible general guidance and insight into future rational design of more metal-oxo clusters protected silver clusters or even other coinage metal nanoclusters.     

Synthesis of orthogonally protected (R)- and (S)-2-methylcysteine via an enzymatic desymmeterization and Curtius rearrangement

A synthesis of differentially protected (R)- and (S)-2-methylcysteines is described. Monomethylation of dimethylmalonate followed by alkylation with tert-butylchloromethyl sulfide gave an achiral diester. Desymmeterization by selective hydrolysis of one ester with pig-liver esterase gave the acid in 97% chemical yield and 91% enantiomeric excess. Heating this acid with diphenylphosphoryl azide followed by 4-methoxybenzyl alcohol gave protected (R)-2-methylcysteine. Alternately, the acid and ester groups were interchanged and heated with diphenylphosphoryl azide followed by 4-methoxybenzyl alcohol, giving protected (S)-2-methylcysteine.     

Efficient synthesis of protected cyclopropyl beta-aspartylphosphates

The in situ reaction of protected dehydroamino acids with derivatives of vinyldiazomethane leads to good to excellent yields of vinyl cyclopropanes via 3 + 2 dipolar cycloaddition followed by N(2) extrusion. Chromatographic separation of the cyclopropane diastereomeric products, followed by characterisation by (1)H NMR and X-ray crystallography allowed the cis and trans diastereomers to be easily identified. Oxidative cleavage of the vinyl moiety then led directly to protected cyclopropane aspartic acid derivatives in three steps from commercially available materials. These compounds were converted to protected methylenephosphonate, difluoromethylenephosphonate and phosphoramidate analogues of [small beta]-aspartyl phosphate.     

A new base-catalyzed cleavage reaction for the preparation of protected peptides

A new base-catalyzed elimination reaction employing the hindered, non-nucleophilic bases tetramethylguanidine or 1,8-diazabicyclo-[5.4.0.]undec-7-ene has been developed for the removal of protected peptides from a 2-[4-(hydroxymethyl)phenyl-acetoxy]propionyl-resin. The proposed reaction mechanism involved cleavage of the ester bond between the peptide and resin via a base-catalyzed elimination. The protected peptide-resin cleavage reaction is mild, rapid and proceeds in good yield with a very simple work- up procedure. Four protected peptide-resins varying in size from seven to sixteen residues were prepared using the 2-[4-(hydroxymethyl)phenyl-acetoxy]- propionyl-resin and then cleaved in the protected form to demonstrate the utility of the new cleavage technique. The protected peptide cleavage products can be used in the preparation of larger peptides by fragment condensation.     

Synthesis and configurational assignment of the amino alcohol in the eastern fragment of the GE2270 antibiotics by regio- and stereoselective addition of 2-metalated 4-bromothiazoles to alpha-chiral electrophiles

A synthesis of the eastern fragment of the thiazole peptide GE2270 A (1) has been developed. The synthetic approach relies on the regioselective functionalization of 2,4-dibromothiazole (5) via metalation and nucleophilic addition (at C2) or palladium-mediated cross-coupling (at C2 or C4). The stereochemistry at the N-bearing stereocenter was established by coupling of 2-metalated 4-bromothiazoles (4) to enantiomerically pure mandelic acid derivatives. Both the erythro (2) and threo (3) configurated amino alcohols were prepared with high diastereoselectivities depending on the electrophile employed. More specifically, the threo-configurated (S,R)-4-bromothiazolyl beta-amino alcohol 6 was synthesized from O-TBS protected (R)-mandelonitrile in 62% yield. Its N-PMB protected (R,S)-enantiomer 20 was obtained from O-TBS protected (S)-mandelic aldehyde in 67% yield. The erythro-configurated (S,S)-4-bromothiazolyl beta-amino alcohol 29 was prepared from O-TBS protected (S)-ethyl mandelate in four steps and 33% overall yield. The bithiazole moiety in the desired products 2 and 3 was finally established by the regioselective Negishi coupling of 2,4-dibromothiazole (5) and the 4-zincated, N-Boc protected thiazole derivatives of the diastereomeric 4-bromothiazolyl beta-amino alcohols 6 and 29.     

Synthesis of diazahexathia-24-crown-8 derivatives and structures of Ag+ complexes

Diazahexathia-24-crown-8 (2) has been isolated from the reaction mixture during the preparation of monoazatrithia-12-crown-4 (1). When N-Boc protected bis(2-chloroethyl)amine was employed as a starting material, N-Boc protected monoazatrithia-12-crown-4 (3) and N-Boc protected diazahexathia-24-crown-4 (4) were separated easily. Double-armed diazahexathia-24-crown-8 having two 3',5'-dichlorobenzyl groups (5a) or two 2-phenylethyl groups (5b) were also prepared using reductive amination. The stoichiometry and detailed structures of the Ag+ complexes with and were investigated by 1H NMR titration experiments and X-ray crystallography.     

A practical synthesis of L-ribose

L-Ribose was synthesized by a simple four-step method with overall yield of 76.3% from a protected L-arabinose derivative, which is a compatible intermediate for the synthesis of L-deoxyribose. The key step of this strategy is the Swern oxidation and subsequent stereoselective reduction accompanied by inversion of the 2-hydroxy group of protected L-arabinose.     

An efficient synthesis of the protected carbohydrate moiety of Brasilicardin A

A synthesis of the protected carbohydrate moiety 2 of Brasilicardin A starting from l-rhamnose and d-glucosamine is described. The disaccharide was synthesized using a TMSOTf-mediated glycosylation of the 2-phthalimido-2-deoxyglucose donor 5 and the 3-hydroxyl group of the protected L-rhamnose derivative 4, which already bears the 3-hydroxybenzoate unit. The imidate 2 was coupled via TMSOTf-mediated glycosidation with cholesterol as a model aglycone followed by the selective cleavage of all the acetate groups to give the Brasilicardin A analogue 16.     

The Friedel-Crafts allylation of a prenyl group stabilized by a sulfone moiety: expeditious syntheses of ubiquinones and menaquinones

An efficient synthetic method for the protected p-hydroquinone compounds 4 containing the C5 trans allylic sulfone moiety has been developed by the direct Friedel-Crafts allylation of the protected dihydroquinone 2 with 4-chloro-2-methyl-1-phenylsulfonyl-2-butene (7a) or 4-hydroxy-2-methyl-1-phenylsulfonyl-2-butene (7b). Expeditious total syntheses of coenzyme Q-10 and vitamin K2(20) have been demonstrated from these valuable key compounds 4a and 4b.     

Stereoselective Synthesis of N~1-Lyxitol Inosine Derivative

Cyclic ADP-ribose (cADPR) 1 (Figure 1), a intracellular Ca2+-mobilizing messenger, is of great interest because of its significant importance in the signal transduction1. However, the biological as well as chemical instability of cADPR limits the studies of its physiological role, at least in some aspect2. Recently, Shuto et.al.3 constructed a mimic of cADPR, cyclic IDP-carbocyclic-ribose 2, in which the 4'-oxo in furanose is substituted by a methylene group and the stability of 2 is i…     

Pyridylethyl: A versatile protecting group. Part II. The protection of heterocyclic N-H groups

Pyrrole, indole, carbazole and imidazole have been protected as N-[2-(4-pyridyl)ethyl] derivatives. Deprotection occurred under mild conditions after quaternisation. 3-Bromoindole was prepared by bromin-ation of the protected parent indole.     

Synthese von selektiv N- funktionalisierten Polyamin-Derivaten

Synthesis of Selectively N-Functionalized Polyamine Derivatives A threefold differently protected derivative 8 of the triamine spermidine ( 2 ) has been prepared in three steps starting from propane-1,3-diamine ( 1 ). The protected spermidine derivative 8 was converted to its spermine analogue 12 , a useful polyamine intermediate. In a convergent way, the fourfold differently protected derivative 18 of the tetraamine spermine ( 3 ) has been obtained by coupling the two different and separately prepared propane-1,3-diamine units 15 and 17 . Spermidine derivative 19 and spermine derivative 20 , both selectively protected at both primary amino groups, have been Prepared from the free polyamines 2 and 3 , respectively, in a direct approach.     

Synthesis of beta-cyclopropylalanines by photolysis of diacyl peroxides

[reaction: see text] Photolysis at 254 nm of neat (no solvent) unsymmetrical diacyl peroxides derived from cyclopropane carboxylic acids and l-aspartic acid generates protected beta-cyclopropylalanines in reasonable yields. Orthogonally protected 3-(trans-2-aminocyclopropyl)alanine (21), a key constituent of the antitumor agent belactosin A, as well as protected hypoglycin A (26), a causative agent of Jamaican vomiting sickness, is synthesized by this approach with coupling of the intermediate substituted cyclopropyl radicals proceeding predominantly with retention of configuration (dr >or= 95:5).     

Addition of difluorocarbene to 3',4'-unsaturated nucleosides: synthesis of 2'-deoxy analogues with a 2-oxabicyclo[3.1.0]hexane framework

Treatment of protected 2'-deoxy-3',4'-unsaturated nucleosides derived from adenosine and uridine with difluorocarbene [generated from bis(trifluoromethyl)mercury and sodium iodide] gave fused-ring 2,2-difluorocyclopropane compounds. Stereoselective alpha-face addition to the dihydrofuran ring resulted from hindrance by the protected beta-anomeric nucleobases. A protected uracil compound was converted smoothly into the cytosine derivative via a 4-(1,2,4-triazol-1-yl) intermediate. Removal of the protecting groups gave new difluorocyclopropane-fused nucleoside analogues. The solid-state conformation of the nearly planar furanosyl ring in the uracil compound had a shallow 2E pucker, and a more pronounced 1E conformation was present in the furanosyl ring of the cytosine derivative.     

Nucleosides and Nucleotides. Part 17. A simple preparation of protected deoxynucleoside-3'-phosphates

A simple method for the preparation of fully protected 2′-deoxynucleoside-3′-phosphates is described. The main step, phosphorylation of partially protected deoxynucleosides, is performed with the monofunctional reagent p-chlorophenyl (2-cyanoethyl) phosphochloridate³) ( 2 ) in dioxane. This reagent is quickly prepared from readily accessible p-chlorophenyl phosphodichloridate by reaction with 3-hydroxypropionitrile and triethylamine in dioxane or ether. The crude reagent is used directly for phosphorylation. After chromatography, protected deoxynucleoside-3′-phosphates were isolated in yields of 80–87%. The method described here, which has been optimized in detail, represents a simple alternative to published methods.     

Stereochemical course of the reductive spiroannulations of N-Boc and N-benzyl 2-cyanopiperidines

The stereochemical outcome of spiroannulations of N-protected 2-lithiopiperidines (generated by lithium di-tert-butyl biphenylide (LiDBB) mediated reductive lithiation of 2-cyanopiperidines) was investigated using deuterium labeled side-chains containing phosphate leaving groups. High stereoselectivity was observed when benzyl (Bn) protected 2-cyanopiperidines were employed, while tert-butoxycarbonyl (Boc) protected 2-cyanopiperidines afforded lower selectivity. Models are proposed to rationalize the results of this study.     

保护的预酯化紫杉醇侧链的合成

以市场可购得的（2R,3S）-苯基异丝氨酸盐酸盐为起始原料,通过在甲醇的氯化亚砜溶液中进行酯化反应,及随后对氨基进行苯甲酰化,氨基羟基的环化保护,最后对其酯进行水解,合成得到保护的预酯化的紫杉醇侧链．整个过程无需柱层析操作,适于工业化生产．为制备保护的预酯化紫杉醇侧链提供了一种有效而又实用的合成方法．     

Facile preparation of N-protected 2-alkylidene-1,3-imidazolidines

Stereoselective preparation of unsymmetrically protected 2-alkylidene-1,3-imidazolidines was achieved by the reaction of N,N′-protected ethylenediamine, bromopropynamide, and K₃PO₄ in hot DMF. When N-protected aminoethanol was used in place of the protected ethylenediamine, an oxazolidine derivative was produced.     

Nucleosides. Part LV. Efficient synthesis of arabinoguanosine building blocks

From guanosine ( 1 ) as starting molecule, protected arabinoguanosine derivatives such as phosphoramidite precursors and arabinoguanosine ( 18 ) itself were prepared in high yields. Inversion of the configuration at C(2′) was achieved by introduction of the (trifluoromethyl)sulfonyl residue and subsequent displacement by nucleophiles like acetate, bromide, and azide. The guanine moiety was protected at the amide function by the 2-(4-nitrophenyl)ethyl (npe) group on O⁶ and at the NH₂ function by the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) group.