Glyconothio-O-lactones. Part III. Thermolysis of a 4,5-Dihydro-1,2,3- and a 2,5-Dihydro-1,3,4-thiadiazole

Addition of CH₂N₂ to 2,3:5,6-di-O-isopropylidene-1-thio-mannono-1,4-lactone ( 1 ) gave the 2,5-dihydro-1,3,4-thiadiazole 2 and the 4,5-dihydro-1,2,3-thiadiazole 3 . First-order kinetics were observed for the thermolysis of 3 (Scheme 3) at 80–110° in C₆D₅Cl solution and of 2 (Scheme 3) at 20–35° in CDC1₃, respectively. The 1,2,3-thiadiazole 3 led to mixtures of the thiirane 9 , the starting thionolactone 1 , the thiono-1,5-lactone 8 , and the enol ether 7 , while the isomeric 1,3,4-thiadiazole 2 led to mixtures of the anomeric thiiranes 9 and 12 , the O-hydrogen S,O,O-ortholactone α-D - 14 , the S-methyl thioester 15 , the S,S,O-ortholactone 13 , and the 2,3:5,6-di-Oisopropylidene-mannono-1,4-iactone ( 16 ). Pure products of the thermolysis were isolated by semipreparative supercritical fluid chromatography (SFC), whereas preparative HPLC led to partial or complete decomposition. Thus, the β-D -mannofuranosyl β-D -mannofuranoside 10 , contaminated by an unknown S species, was isolated by preparative HPLC of the crude product of thermolysis of 3 at 115–120° and partially transformed in CD₃OD solution into the symmetric di(α-D -mannofuranosyl) tetrasulfide 11 . Its structure was evidenced by X-ray analysis. Similarly, HPLC of the thermolysis product of 2 gave the enethiol 17 , the sulfide 19 , and the mercapto alcohol 18 as secondary products. Thermolysis of the thiirane 9 at 110–120° (Scheme 4) led to the anomeric thiirane 12 which was transformed into mixtures of the enethiol 17 and the enol ether 7. Addition of H₂O to 17 and 7 gave the corresponding hemiacetals 18 and 20. The mechanism of the thermolysis of the dihydrothiadiazoles 2 and 3 , and the thiiranes 9 and 12 is discussed.     

Preparation and Transmetallation of a Triphenylstannyl β-D-Glucopyranoside: A highly stereoselective route to β-D-C-glycosides via glycosyl dianions

The triphenylstannyl β-D -glucopyranoside 4 was synthesized in one step from the 1,2-anhydro-α-D -glucopyranose 3 with (triphenylstannyl)lithium (Scheme 1). Transmetallation of 4 with excess BuLi, followed by quenching the dianion 7 with CD₃OD gave (1S)-1,5-anhydro-3,4,6-tri-O-benzyl-[1-²H]-D - glucitol ( 8 ) in 81% yield (Scheme 2). Trapping of 7 with benzaldehyde, isobutyraldehyde, or acroleine gave the expected β-D -configurated products 11, 12 , and 13 in good yields. Preparation of C-acyl glycosides from acid chlorides, such as acetyl or benzoyl chloride was not practicable, but addition of benzonitrile to 7 yielded 84% of the benzoylated product 14 . Treatment of 7 with MeI led to 15 (30%) along with 40% of 18 , C-alkylation being accompanied by halogen-metal exchange. Prior addition of lithium 2-thienylcyanocuprate increased the yield of 15 to 50% and using dimethyl sulfate instead of MeI led to 77% of 15 . No α-D -anomers could be detected, except with allyl bromide as the electrophile, which yielded in a 1:1 mixture of the anomers 16 and 17 .     

Regio‐ and Stereoselectivity in the Lewis Acid‐ and NaH‐Induced Reactions of Thiocamphor with (R)‐2‐Vinyloxirane

The reaction of the enolizable thioketone (1R,4R)‐thiocamphor (= (1R,4R)‐1,7,7‐trimethylbicyclo[2.2.1]heptane‐2‐thione; 1 ) with (R)‐2‐vinyloxirane ( 2 ) in the presence of a Lewis acid such as SnCl₄ or SiO₂ in anhydrous CH₂Cl₂ gave the spirocyclic 1,3‐oxathiolane 3 with the vinyl group at C(4′), as well as the isomeric enesulfanyl alcohol 4 . In the case of SnCl₄, an allylic alcohol 5 was obtained in low yield in addition to 3 and 4 (Scheme 2). Repetition of the reaction in the presence of ZnCl₂ yielded two diastereoisomeric 4‐vinyl‐1,3‐oxathiolanes 3 and 7 together with an alcohol 4 , and a ‘1 : 2 adduct’ 8 (Scheme 3). The reaction of 1 and 2 in the presence of NaH afforded regioselectively two enesulfanyl alcohols 4 and 9 , which, in CDCl₃, cyclized smoothly to give the corresponding spirocyclic 1,3‐oxathiolanes 3, 10 , and 11 , respectively (Scheme 4). In the presence of HCl, epimerization of 3 and 10 occurred to yield the corresponding epimers 7 and 11 , respectively (Scheme 5). The thio‐Claisen rearrangement of 4 in boiling mesitylene led to the allylic alcohol 12 , and the analogous [3,3]‐sigmatropic rearrangement of the intermediate xanthate 13 , which was formed by treatment of the allylic alcohol 9 with CS₂ and MeI under basic conditions, occurred already at room temperature to give the dithiocarbonate 14 (Schemes 6 and 7). The presented results show that the Lewis acid‐catalyzed as well as the NaH‐induced addition of (R)‐vinyloxirane ( 2 ) to the enolizable thiocamphor ( 1 ) proceeds stereoselectively via an S_N2‐type mechanism, but with different regioselectivity.     

Electrochemical Fluorination of Dithiocarbonates Using a Triarylamine Mediator

Electrochemical oxidation of O-(4-chlorobenzyl) S-methyl dithiocarbonate using tris(2,4-dibromophenyl)amine as a redox mediator was studied by cyclic voltammetric measurements. The triarylamine mediated anodic fluorodesulfurization of O-(4-chlorobenzyl) and O-(4-bromobenzyl) S-methyl dithiocarbonates provided 4-chloro- and 4-bromobenzyl fluorides, respectively in moderate yields. On the other hand, similar anodic fluorination of O-(2-phenethyl) S-octyl dithiocarbonate and O-(4-bromophenyl) S-methyl dithiocarbonate afforded 2-phenethyl trifluoromethyl ether and difluoro(methylthio)methyl 4-bromophenyl ether, respectively. Mechanistic aspects are also discussed.     

Selenium‐Containing Heterocycles from Isoselenocyanates: Synthesis of 5‐Amino‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐selones

The reaction of S‐methylisothiosemicarbazide hydroiodide (=S‐methyl hydrazinecarboximidothioate hydroiodide; 1 ), prepared from thiosemicarbazide by treatment with MeI in EtOH, and aryl isoselenocyanates 5 in CH₂Cl₂ affords 3H‐1,2,4‐triazole‐3‐selone derivatives 7 in good yield (Scheme 2, Table 1). During attempted crystallization, these products undergo an oxidative dimerization to give the corresponding bis(4H‐1,2,4‐triazol‐3‐yl) diselenides 11 (Scheme 3). The structure of 11a was established by X‐ray crystallography.     

Stereoselektive Alkylierung an C(α) von Serin,Glycerinsäure,Threonin und Weinsäure über heterocyclische Enolate mit exocyclischer Doppelbindung

Steroselective Alkylation at C(α) of Serine, Clyceric Acid, Threonine, and Tartaric Acid Involving Heterocyclic Enolates with Evocyelic Double Bonds The chiral, non-racemic title acids are converted to methyl dioxolane-(cf. 13 ), oxazoline-( 4 ) and oxazolidinecarboxylates (cf. 9 ). Deprotonation by Li(i-Pr) ₂N at dry-ice temperature gives solutions of the lithium enolates A–D With exocyclic enolate double bonds. These are stable crough with respect to β-elimination (Scheme 1) to be alkylated with or without cosolvents such as HMPA or DMPU The products are formed in good to excellent yields and, with the exception of the tartrate-derived acetonlde (see Scheme 2), with diastereoselectivities above 90%. While the tartrate-and threonine-derived enolates ( A and B , resp.) are chiral due to the second stereogenic center of the precursors, the serine- and glyceric-acid-derived enolates ( A and B , resp.) are chiral due to the second sterogenic center of the precursors, the serine-nd glyceric-acid-derived enolates are non-racemic due to a tert butyl-substituted (pivalaldehyde-derived) acetal center ( C and D , resp.). The products of alkylation can be hydrolyzed to give α-branched tartaric acid (Scheme 2), allothreonine (Scheme 3), serine (Scheme 4), and glyceric-acid derivatives (Scheme 5) with quaternary stereogenic centers. The configurations of the products are determined by NOE-NMR measurements and by chemical correlation. These show that the dioxolane-derived enolates A and D are alkylated preferentially from that face of the ring which is already substituted (‘syn’-attack), while the dihydrooxazol-and oxazolidine-derived enolates B and C are alkylated from the opposite face (‘anti’-attack). The ‘syn’-attack is postulated to arise from strong folding of the heterocyclic ring due to electronic repulsion between the enolate π-system and non-bonding electron pairs on the heteroatoms (see Scheme 6).     

Glycosylidene Carbenes. Part 13. Synthesis and thermolysis of representative 1-azi-glycoses

In the context of the hypothesis postlating a heterolytic cleavage of a C? N bond during thermolysis of alkoxydiazirines (Scheme 1), we report the preparation of the diazirines 4 , 5 , 7 , and 8 , the kinetic parameters for the thermolysis in MeOH of the diazirines 1 and 4–9 , and the products of their thermolysis in an aprotic environment. The diazirines 4 , 57 , and 8 (Scheme 2–5) were prepared from the known hemiacetals 10 , 19 , 34 (prepared from 31 in an improved way), and 42 according to an established method. The oximes 11 , 20 , 35 , and 43 were obtained from the corresponding hemiacetals as (E/Z)-mixtures; 43 was formed together with the cyclic hydroxylamine 44 . Oxidation of 11 , 35 , and 43 (N-chlorosuccinimide/1,8-diazabicyclo[5.4.0]undec-7-ene (NCS/DBU) or NaIO₄) gave good yields of the (Z)-hydroximolactones 12 , 36 , and 45 , while the oxime 20 led to a mixture of the (E)- and (Z)-hydroximolactones 21 and 22 , which adopt different conformations. Their configuration was assigned, inter alia, by a comparison with the enol ethers 28 and 29 , which were obtained, together with 30 , from the reaction of the diazirine 5 with benzaldehyde and PBu₃. Treatment of the hydroximolactone O-sulfonates 13 , 23 , 37 , and 46 with NH₃/MeOH afforded the diaziridines 15 , 25 , 38 , and 47 in good yields, while the (E)-sulfonate 24 decomposed readily. Oxidation of the diaziridines gave 4 , 5 , 7 , and 8 , respectively. Thermolysis of the diazirines 1 and 4–9 in MeOH yielded the anomeric methyl glycosides 50/51 , 16/17 , 26/27 , 52/53 , 39/40 , 48/49 , and 54/55 , respectively. A comparison of the kinetic data of the thermolysis at four different temperatures shows the importance of conformational and electronic factors and is compatible with the hypothesis of a heterolytic cleavage of a C? N bond. An early transition state is evidenced by the absence of torsional strain by an annulated 1,3-dioxane ring. Thermolysis of 1 in MeCN at 23° led mostly to the diasteroisomeric (Z,Z)-, (E,E)-, and (E,Z)-lactone azines 56 , 57 , and 58 (Scheme 6), which convert to 56 under mild conditions, and to 59 (3%). The benzyloxyglucal 59 was obtained in higher yields (18%), together with 44% of 56–58 , by thermolysis of solid 1 . Similarly, thermolysis at higher temperatures of 4 in toluene, THF, or dioxane and of 9 in CH₂Cl₂ or THF yielded the (Z,Z)-lactone azines 60 and 61 , respectively, the latter being accompanied by the dihydro-oxazole 62 .     

Succinonitrile Activated by Thiating Agents as Precursor of Bis-cyclic Amidines, Tectons for Molecular Engineering

Summary. Modification of the thio-Pinner’s method via in situ activation of a nitrile by thiating agents, S₈, P₄S₁₀, Lawesson reagent, or Na₂S·9H₂O, was applied in the syntheses of bis(4,5-dihydro-1H-imidazol-2-yl)alkanes and bis(1,4,5,6-tetrahydropyrimidin-2-yl)alkanes.     

Peptide Enolates. C-Alkylation of Glycine Residues in linear tri-, tetra-, and pentapeptides via dilithium azadienediolates

The Boc-protected tripeptides Boc-Val-Gly-Leu-OH ( 1 ), Boc-Leu-Sar-Leu-OH ( 2 ), Boc-Leu-Gly-MeLeu-OH ( 3 ), and Boc-Val-BzlGly-Leu-OMe ( 64 ), tetrapeptide Boc-Leu-Gly-Pro-Leu-OH ( 9 ), and pentapeptides Boc-Val-Leu-Gly-Abu-Ile-OH ( 4 ), Boc-Val-Leu-Sar-MeAbu-Ile-OH ( 5 ), Boc-Val-Leu-Gly-MeAbu-Ile-OH ( 6 ), Boc-Val-Leu-BzlGly-BzlAbu-Ile-OH ( 7 ), and Boc-Val-Leu-Gly-BzlAbu-Ile-OH ( 8 ) are prepared by conventional methods (Schemes 4–7) or by direct benzylation of the corresponding precursors (Scheme 8). Polylithiations in THF give up to Li₆ derivatives containing glycine, sarcosine or N-benzylglycine Li enolate moieties ( A–H ). The polylithiated systems with a dilithium azadienediolate unit ( C, F–H ) are best generated by treatment with t-BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (R)-configuration (i.e. a D -amino-acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i-PrI, allyl and benzyl bromide, ethyl bromoacetate, CO₂, and Me₂S₂ (Schemes 11–13). No epimerizations of the starting materials (racemization of the amino-acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock-freezing or by very slow cooling from room temperature to ?75° before lithiation, give rise to different stereoselectivities (Scheme 11). The latter and the yields can also be influenced by tempering the lithiated species before (Scheme 9) or after addition of the electrophiles (Scheme 12). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80–95%). The results described are yet another demonstration that peptides may be backbone-modified through Li enolates, and that whole series of analogous peptide derivatives with various side chains may thus be produced from a given precursor.     

Deoxy-nitrosugars. 17th communication. Synthesis of ketose-derived nucleosides from 1-deoxy-1-nitroribose

A new approach to ketose-derived nucteosides is described. It is based upon a chain elongation of 1-deoxy-1-nitroaldoses, followed by activation of the nitro group as a leaving group, and introduction of a pyrimidine or purine base. Thus, the nitroaldose 7 was prepared from 3 by pivaloylation (→ 4 ), synthesis of the anomeric nitrones 5/6 , and ozonolysis of 6 (Scheme 1). Partial hydrolysis of 4 yielded 8/9 , which were characterized as the acetates 10/11 and transformed into the nitrones 12/13 . Ozonolysis of 12/13 gave 14/15 , which were acetylated to 16/17 . Henry reaction of 7 lead to 19 and 20 , which were acetylated to 21 and 22 (Scheme 2). Michael addition of 7 to acrylonitrile and to methyl propynoate yielded the anomers 23/24 and 25/26 , respectively. Similar reactions of 16/17 were prevented by a facile β-elimination. Therefore, the nitrodiol 15 was transformed into the orthoesters 27 and then, by Henry reaction, partial hydrolysis, and acetylation, into 28 and 29 (Scheme 2). The structure of 19 was established by X-ray analysis. It was the major product of the kinetically controlled Henry reaction of 7 . Similarly, the β-D-configurated nitroaldoses 23 and 25 were the major products of the Michael addition. This indicates a preferred ‘endo’-attack on the nitronate anion derived from 7 . AMI calculations for this anion indicate a strong pyramidalization at C(1), in agreement with an ‘endo’-attack. Nucleosidation of 21 by 31 afforded 32 and 33 . Yields depended strongly upon the nature and the amount of the promoter and reached 77% for 33 , which was transformed into 34 , 35 , and the known ‘psicouridine’ ( 36 ; Scheme 3). To probe the mechanism, the trityl-protected 30 was nucleosidated yielding 37 , or 37 and 38 , depending upon the amount of FeCl₃. Nucleosidation of the nitroacetate 28 was more difficult, required SnCl₂ as a promoter, and yielded 39 and 40 . The β-D-anomer 40 was transformed into 36 . Nucleosidation of 23 (SnCl₄) yielded the anomers 41 and 42 , which were transformed into 43 and 44 , and hence into 45 and 46 (Scheme 4). Similarly, nucleosidation of 25 yielded 47 and 48 , which were deprotected to 49 and 50 , respectively. The nucleoside 49 was saponified to 51 . Nucleosidation of 21 by 52 (SnCl₂) afforded the adenine nucleosides 53 and 54 (Scheme 5). The adenine nucleoside 53 was deprotected (→ 55 → 56 ) to ‘psicofuranine’ (1), which was also obtained from 58 , formed along with 57 by nucleosidation of 28 . The structure and particularly the conformation of the nitroaldoses, nitroketoses, and nucleosides are examined.     

Fast and reversible migrations of N,S-centered groups around the perimeter of cyclopropene and cycloheptatriene rings

The kinetics and mechanism of circumambulatory rearrangements of N-centered (NCS) and S-centered (SPh, SC₃Ph₃, SC(OEt)=S) groups in corresponding derivatives of 1,2,3-triphenylcyclopropene and cycloheptatriene were studied by dynamic¹H and¹³C NMR spectroscopy. Migrations of the isothiocyanate group occur by the dissociation-recombination mechanism with intermediate formation of a tight ionic pair. Migrations of the phenylthio group around the perimeter of cyclopropene and cycloheptatriene rings occur by the 1,2-shift mechanism. It was found that rearrangements of theO-ethyl dithiocarbonate group inS-(1,2,3-triphenylcyclopropen-3-yl)-O-ethyl dithiocarbonate occur by the 3,3-sigmatropic shift mechanism. The molecular and crystal structure ofO-ethylS-(1,2,3-triphenylcyclopropen-3-yl) dithiocarbonate was studied by X-ray analysis.     

Reduktive Co-Alkylierung von Heptamethyl-cobyrinat mit dem Methylthiomalonat (S)-Methyl-3-bromo-2-[(ethylthio) carbonyl]-2-methylpropanoat

Reductive Co Alkylation of Heptamethyl Cobyrinate with the Methylthiomalonate (S)-Methyl 3-Bromo-2-[(ethylthio)carbonyl]-2-methylpropanoate The methylthiomalonate(?)-(S)-Methyl 3-bromo-2-[(ethylthio)carbonyl]-2-methylpropanoate( 5a )was prepared from dimethyl methylmalonate in five steps via the stereospecific cleavage of the (pro-S)-ester group of 1 with pig-liver esterase in an overall yield of 26.5% (Scheme 4a). Reductive Co alkylation of heptamethyl Coβ-perchlorato cob (II)yrinate ( 8 ) with 5a by electrosynthesis lead to the alkylcobalt complex 9a in 40% yield (Scheme 4b). The O2-dependent reactions of the methyhnalonyl fragment produced by photolysis of 9a and its deuterated derivative 9c are reported (Scheme 5).     

Chiral Borate Esters in Asymmetric Synthesis. Part 2

Asymmetric catalytic activity of the chiral spiroborate esters 1 – 9 with a O₃BN framework (see Fig. 1) toward borane reduction of prochiral ketones was examined. In the presence of 0.1 equiv. of a chiral spiroborate ester, prochiral ketones were reduced by 0.6 equiv. of borane in THF to give (R)‐secondary alcohols in up to 92% ee and 98% isolated yields (Scheme 1). The stereoselectivity of the reductions depends on the constituents of the chiral spiroborate ester (Table 2) and the structure of the prochiral ketones (Table 1). The configuration of the products is independent of the chirality of the diol‐derived parts of the catalysts. A mechanism for the catalytic behavior of the chiral spiroborate esters (R,S)‐ 2 and (S,S)‐ 2 during the reduction is also suggested.     

Structural Chemistry of Methyl- and Allylpalladium(II) Complexes Containing Chiral Thioether Auxiliaries

The molecular structures of three Pd^II compounds are reported: a) the two [PdCl(Me)] complexes 7a and 8a each containing a different chiral N,S-chelate based on {[(dihydrooxazolyl)phenyl]methyl}-thioglucose backbones, e.g., chloro({2-[(4S)-4,5-dihydro-4-isopropyloxazol-2-yl-κN]phenyl}methyl 2,3,4,6-tetra-O-acetyl-1-(thio-κS)-β-D -glucopyranoside)methylpalladium(II) ( 7a ) and b) one [Pd(η³-C₃H₅)(P-S)]⁺ cation in which the P,S-chelate stems from a phosphinoferrocene and thioephedrine-derived thioether donor, i.e., [(S)-1-(diphenylphosphino-κP)-2-((1R)-1-{[(1R,2S)-1-phenyl-2-(piperidin-1-yl)propyl]thio-κS}ethyl)ferrocene] (η³-prop-2-enyl)palladium trifluoromethanesulfonate ( 11 ). In the methylpalladium compounds 7a and 8a the thioglucose-κS moiety is pseudo-axial (Figs. 2 and 3), whereas in the allyl complex, the thioephedrine-κS moiety is markedly pseudo-equatorial (Fig. 5). It is suggested, based on these results, that the shape (chiral pocket) of such coordinated chiral thioethers may not be readily predictable.     

Attempted Synthesis of the Imidazylate of an α-Hydroxylactone Results in Unexpected Chlorination: Synthesis and X-Ray Crystal Structure of 5-Chloro-5-deoxy-1,2-O-isopropylidene-β-l-idurono-6,3-lactone

Attempted synthesis of the imidazylate derivative of 1,2-O-isopropylidene-α-D-glucurono-6,3-lactone (2) via treatment with sulfuryl chloride in the presence of excess imidazole in DMF at either –40°C or –70°C resulted in the unexpected formation of 5-chloro-5-deoxy-1,2-O-isopropylidene-β-l-idurono-6,3-lactone (7). Chloride 7 presumably forms via the rapid S_N2 displacement by a chloride ion of an initially formed chlorosulfate ester intermediate, which is evidently unusually reactive. The identity of the product was confirmed by a single-crystal X-ray structure determination.     

Glycosylidene Carbenes. Part 31

The diastereoselectivity of the addition of NH₃ and MeNH₂ to glyconolactone oxime sulfonates and the structures of the resulting N‐unsubstituted and N‐methylated glycosylidene diaziridines were The ¹⁵N‐labelled glucono‐ and galactono‐1,5‐lactone oxime mesylates 1* and 9* add NH₃ mostly axially (>3 : 1; Scheme 4), while the ¹⁵N‐labelled mannono‐1,5‐lactone oxime sulfonate 19* adds NH₃ mostly equatorially (9 : 1; Scheme 7). The ¹⁵N‐labelled mannono‐1,4‐lactone oxime sulfonate 30* adds NH₃ mostly from the exo side (>4 : 1; Scheme 9). The configuration of the N‐methylated pyranosylidene diaziridines 17, 18, 28 , and 29 suggests that MeNH₂ adds to 1, 9, 19 , and 23 mostly to exclusively from the equatorial direction (>7 : 3; Schemes 5 and 8). The mannono‐1,4‐lactone oxime sulfonate 30 adds MeNH₂ mostly from the exo side (85 : 15; Scheme 10), while the ribo analogue 37 adds MeNH₂ mostly from the endo side (4 : 1; Scheme 10). Analysis of the preferred and of the reactive conformers of the tetrahedral intermediates suggests that the addition of the amine to lactone oxime sulfonates is kinetically controlled. The diastereoselectivity of the diaziridine formation is rationalized as the result of the competing influences of intramolecular H‐bonding during addition of the amines, steric interactions (addition of MeNH₂), and the kinetic anomeric effect. The diaziridines obtained from 2,3,5‐tri‐O‐benzyl‐D ‐ribono‐ and ‐D ‐arabinono‐1,4‐lactone oxime methanesulfonate ( 42 and 48 ; Scheme 11) decomposed readily to mixtures of 1,4‐dihydro‐1,2,4,5‐tetrazines, pentono‐1,4‐lactones, and pentonamides. The N‐unsubstituted gluco‐ and galactopyranosylidene diaziridines 2, 4, 6, 8 , and 10 are mixtures of two trans‐substituted isomers ( S / R ca. 19 : 1, Scheme 2). The main, (S,S)‐configured isomers S are stabilised by a weak intramolecular H‐bond from the pseudoaxial NH to RO? C(2). The diaziridines 12 , derived from GlcNAc, cannot form such a H‐bond; the (R,R)‐isomer dominates ( R / S 85 : 15; Scheme 3). The 2,3‐di‐O‐benzyl‐D ‐mannopyranosylidene diaziridines 20 and 22 adopt a ⁴C₁ conformation, which does not allow an intramolecular H‐bond; they are nearly 1 : 1 mixtures of R and S diastereoisomers, whereas the ^OH₅ conformation of the 2,3:5,6‐di‐O‐isopropylidene‐D ‐mannopyranosylidene diaziridines 24 is compatible with a weak H‐bond from the equatorial NH to O? C(2); the (R,R)‐isomer is favoured ( R / S ≥7 : 3; Scheme 6). The mannofuranosylidene diaziridine 31 completely prefers the (R,R)‐configuration (Scheme 9).     

A New Stereospecific Synthesis of 1,2,4-Trideoxy-1,4-Imino-D-Erythro-Pentitol

ABSTRACT

1,2,4-Trideoxy-1,4-imino-D-erythro-pentitol [(2R,3S)-3-hydroxy-2-hydroxyme-thylpyrrolidine] (4) was synthesised from 2,5-di-O-tosyl-D-ribono-1,4-lactone in 42% overall yield. The key steps were deoxygenation at C-2 and a stereospecific inversion of the configuration at C-4. Compound 4 inhibited α-D-glucosidase (K_i = 25 μM) and β-D-glucosidase (K_i = 80 μM).     

Synthese eines cyclischen Depsipeptides mittels Amidcyclisierung

Synthesis of a Cyclic Depsipeptide via an Amide Cyclization The synthesis of (S)-Pms-(R)-Pro-(S)-Ala-Aib-N(CH₃)₂ ( 12 ) has been achieved according to Scheme 3. For the formation of fragment 11 , the reaction of Z-alanine (Z = benzyloxycarbonyl) and 3-dimethylamino-2,2-dimethyl-2-azirine ( 1 ) has been used, whereby 1 serves as an aminoisobutyric-acid dimethylamide (aib-N(CH₃)₂) equivalent. Treatment of a suspension of 12 in toluene with HCl gas at 100° led to the cyclic depsipeptide 13 in 72% yield (Scheme 4). In presence of water, the acid 14 was isolated as the sole product. A mechanism for the formation of 13 and 14 via an oxazolinone intermediate, is postulated in Scheme 4.     

Cob(I)alamin als Katalysator, 5. Mitteilung [1]. Enantioselektive Reduktion α,β-ungesättigter Carbonylderivate

Cob(I)alamin as Catalyst. 5. Communication [1]. Enantioselective Reduction of α,β-Unsaturated Carbonyl Derivatives The cob(I)alamin-catalyzed reduction of an α,β-unsaturated ethyl ester in aqueous acetic acid produced the (S)-configurated saturated derivative 2 with an enantiomeric excess of 21%. The starting material 1 is not reduced at pH = 7.0 in the presence of catalytic amounts of cob(I)alamin (see Scheme 2). It is shown that the attack of cob(I)alamin and not of cob(II)alamin, also present in Zn/CH₃COOH/H₂O, accounts for the enantioselective reduction observed. All the (Z)-configurated starting materials 1 , 3 , 5 , 7 , 9 and 11 have been transformed to the corresponding (S)-configurated saturated derivatives 2 , 4 , 6 , 8 , 10 and 12 , respectively. The highest enantiomeric excess revealed to be present in the saturated product 12 (32,7%, S) derived from the (Z)-configurated methyl ketone 11 (see Scheme 3 and Table 1). The reduction of the (E)-configurated starting materials led mainly to racemic products. A saturated product having the (R)-configuration with a rather weak enantiomeric excess (5.9%) has been obtained starting from the (E)-configurated methyl ketone 23 (see Scheme 5 and Table 2). The allylic alcohols 16 and 24 have been reduced to the saturated racemic derivative 17 .     

Glycosylidene Carbenes. Part 21. Synthesis of N-tosylglycono-1,4-lactone hydrazones as precursors of glycofuranosylidene carbenes

The N′-(glycofuranosylidene)toluene-4-sulfonohydrazides 5 and 10 (Scheme 1) were prepared in good yields by oxidation (1,3-dibromo-5,5-dimethylhydantoin/Et₃N) of the N′-glycosyltoluene-4-sulfonohydrazides 4 and 9 , which were obtained from 2,3,5-tri-O-benzyl-D -ribose ( 3 ) and 2,3,5-tri-O-benzyl-D -arabinose ( 8 ), respectively, and toluene-4-sulfonohydrazide. The analogous naphthalene-2-sulfonohydrazides 7 and 12 were similarly prepared from 3 and 8 via 6 and 11 . Photolysis in the presence of phenol of the sodium salt 15 (Scheme 2), best generated in situ, yielded the anomeric glycosides 16 , some 5 , and traces of the glycosides (1R)/(1S)- 17 . Photolysis of 15 in THF gave the sulfones α-D /β-D - 18 . Photolysis of 15 (quartz filter) and dimethyl fumarate led to a single cyclopropane 19 , the sulfones α-D /β-D - 18 , and the N-(ribofuranosyl)-N′-(ribofuranosylidene)toluene-4-sulfonohydrazide 20 . Similarly, N-phenylmaleimide afforded the cyclopropanes 21 and 22 . Photolysis of the sodium salt of 10 and phenol afforded the anomeric glycosides α-D /β-D - 23 , the C-glycoside 24 , and the sulfone 25 . Photolytic glycosidation of 15 with N⁶-benzyladenine gave the two nucleosides 26 and 27 (Scheme 3).