Synthesis of N-[2-S -(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-Thio-D-Lactoyl]-L-alanyl-D-isoglutamine

Abstract

N-[2-S-(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-thio-D-lactoyl]-L-alanyl-D-isoglutamine, in which the oxygen atom at C-3 of N-acetylmuramoic acid moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) has been replaced by sulfur, was synthesized from allyl 2-acetamido-2-deoxy-β-D-glucopyranoside (1).

Treatment with sodium acetate of the 3-O-mesylate, derived from 1 by 4,6-O-isopropylidenation and subsequent mesylation, gave allyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-allopyranoside (4). When treated with potassium thioacetate, the 3-O-mesylate, derived from 4, afforded allyl 2-acetamido-3-S-acetyl-2-deoxy-4,6-0-isopropylidence-β-D-glucopyranoside (6). S-Deacetylation of 6, condensation with 2-L-chloropropanoic acid, and subsequent esterification, gave the 3-s[D-1(methoxycarbonyl)ethyl]-3-thio-glucopyranoside derivative (7). Coupling of the acid, derived from 7, with the methyl ester of L-alanyl-D-isoglutamine, and subsequent hydrolysis, yielded the title compound.     

Nonreducing-Sugar Subunit Analogs of Bacterial Lipid a Carrying the Ester-Bound (3R)-3-(Acyloxy)Tetradecanoyl Group

Abstract

In order to elucidate further the relationship between the composition of the fatty acyl groups in the nonreducing-sugar subunit of bacterial lipid A and its biological activity, 3-O-[(3R)-3-(acyloxy)tetradecanoyl]-2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-4-O-phosphono-D-glucose [GLA-63(R, R) and GLA-64(R, R)], and 3-O-[(3R)-3-(acyloxy)tetradecanoyl]-2-deoxy-4-O-phosphono-2-tetradecanamido-D-glucose [GLA-67(R), GLA-68(R) and GLA-69(R)] have been synthesized. Benzyl 2-[(3R)-3-(benzyloxymethoxy)tetradecanamido]-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside (5) and benzyl 2-deoxy-4,6-O-isopropylidene-2-tetradecanamido-β-D-glucopyranoside (6) were each esterified with (3R)-3-dodecanoyloxytetradecanoic acid (1), (3R)-3-tetradecanoyloxytetradecanoic acid (2) or (3R)-3-hexadecanoyloxy-tetradecanoic acid (3), to give 7-11, which were then transformed, by the sequence of deisopropylidenation, 6-O-tritylation and 4-O-phosphorylation, into a series of desired compounds.     

A New Synthesis of 3-Aryl-5-Arylmethylene-2(5H)-Furanones

A recent report about the synthesis of di and tri-substituted 2 (5H)-furanones starting from bromoaldehydes and potassium phenyl-acetate¹ prompts us to report our own studies on the preparation of 3-aryl-5-arylmethylene-2 (5H)-furanones (or butenolides) 1. We have earlier reported² a general method for the synthesis of 1 from phenylpropargyl aldehyde, 2 and arylacetic acids. Although several methods have been reported for the synthesis of the parent compound 1 (R = R₁ = Ph)^3–6, these methods have not been extended to other substituted furanones. Saikachi and Taniguchi⁷ prepared 1 (R = 5-nitro-2-thenyl, R₁ = 2-thenyl and 2-furyl) in 16–17% yields.     

A Convenient Preparation of (R)-7-(3-Benzothienylglycylamido)deacetoxycephalosopranic Acid

An efficient synthesis of (R)-7-(3-benzothienylamido)deacetoxy-cephalosporanic acid (1) is described beginning from (R)-alpha-aminobenzo[b]thiophene-3- acetic acid (2) and 7-amino-3-methyl-3-cephem-4-carboxylic acid (7-ADCA). Good yields were obtained and the procedure is amenable to multikilogram preparations.     

Mono-(BOC)-Protected Diamines. Synthesis of tert-Butyl-N-alkyl-N-(2-aminoethyl)carbamates and tert-Butyl-N-[2-(alkylamino)ethyl] Carbamates

We wish to report preparative pathways to the mono-(BOC)-protected diamines 1a-d and 2a-c.     

Synthesis of Some Spirooxazolidinones

In this communication, we wish to report the synthesis of some new spiro-4-oxazolidinones. Treatment of the potassium salt of 2-methyl-cyclohexane-1,3-dione (1) with α-chloroacetanilides (2 a-c) gave 4-aryl-6-methyl-1-oxa-4-aza-spiro [4,5] deca-3,7-diones (3 a-c); and with α-halopropionanilides (2 d,e), the corresponding 4-aryl-2,6-dimethyl-1-oxa-4-aza-spiro [4,5] deca-3,7-diones (3 d, e) were obtained.     

The structure of cis and trans lsomers of 1-(p-Bromobenzylidene)-2-indanone

Abstract

In this communication we wish to report an interesting case of the isolation and characterization of the cis and trans isomers of 1-(p-bromobenzylidene)-2-indanone and their ketals. Prior to this work, Hoogstreen and Trenner² had reported on the cis and trans isomers of 1-(p-chlorobenzylidene)-2-methyl-5-methoxyindenylacetic acid. The condensation of 2-(N-morpholinyl)-indene (1, prepared by the reaction of 2-indanone³ and morpholine) with P-bromobenzaldehyde was conducted by refluxing them in the presence of acetic acid for 4 hours. Acid hydrolysis of the reaction mixture followed by dry column chrcmatography over sillica gel using a fraction collector afforded two iscmeric monobenzylidenes, compounds 2(36.6%, mp 110–111°)and 3(1.3%, mp 115–116°) and a dibenylidene, compound 4 (8.7%, mp 205°). The relative rations of the mono- and dibenzylidenes seemed to depend on the reaction conditions. Higher yields of the monobenzylidenes 2 and 3 were obtained by conducting the reaction in the presence of UV light. The structures of these monobenzylidenes were established as cis and trans isomers of 1-(p-bromobenzylidenes)-2-indanone on the Basis of elemental analyses and ir and nmr spectroscopy. The ir spectra⁴ (CHCl₃)

of compounds 2 [1725 (c=0), 1620 (c=c)cm^?1] and 3[1710 (c=o), 1570, 1600 (c=c) cm^?1] were consistent with the structures. The molecular ion peaks as well as the fragmentation patterns in the mass spectra of both these compounds were consistent with the assigned structures. Before going into the omr discussion it should be pointed out that treatment of compound 2 with athylene glycol in the presence of p-toluene sulfonic acid produced two ketals, 5 (38.3% mp, 118–120°) and 6 (30.6% mp, 125–126°). As depicted; the ketals 5and 6 were also found (by omr) to be related to each other as cis and trans isomers. Furthermore, each of them could be hydrolyzed with acid to the corresponding monobenzylidenes 2 and 3 without any isomerization. However, UV irradiation of compounds 2 and 3 gave equilibrium mixtures containing both the isomers, indicating isomerization had occurred under photolytic conditions.     

Synthesis of Bioactive Pyrethroid, 3-Phenoxybenzyl 1R-trans-2, 2-Dimethyl-3-(2-chloro-1-propenyl) Cyclopropanecarboxylate

The title compound 1 has been prepared from (+)-3-carene (2) and found to have the same order of activity as its IR-cis isomer 3 reported by us earlier¹ The key intermediate methyl IR-trans-2, 2-dimethyl-3-(2-oxopropyl)cyclopropanecarboxylate (4) has been characterised.     

A Convenient Synthesis of 3-Deoxy-D-gluco-2-octulosonate (D-gluco-KDO)

β-Lithiated acrylates have proven to be versatile pyruvate β-carbanion equivalents which are also useful in D-manno-KDO synthesis. The secondary amine adducts of acetylenedicarboxylate 4 display the same versatility, as demonstrated in this paper. However, on reaction with 2,3:4, 5-di-O-isopropylidene-D-arabinose 6, the diastereofacial selectivity is in favor of the gluco-isomer, thus leading with lithiated compounds 4A, preferentially to α-aminobutenolides 7-(g). The best results were obtained with the morpholine adduct of di-tert.-butyl acetylenedicarboxylate 4d which afforded the gluco-isomer 7d-(g) as an easily separable crystalline material. Its deamination and concomitant deisopropylidenation with trifluoroacetic acid provided the known α-hydroxy-butenolide 8b-(g), which was transformed via decarboxylation product 9-(g) to D-gluco-KDO 10-(g) thus concluding a convert four step synthesis of this compound via crystalline intermediates.     

Stereocontrolled Conversion of 3,5-Dioxopyrrolizidine Into (Z)- and (E)- 5-Acetonylpyrrolizidin-3-ones

Stereocontrolled synthesis of (Z)-5-acetonyl-pyrrolizidin-3-one (4) and (E)-isomer 5 from 3,5-dioxopyrrolizidine 1 is described.     

Synthesis of the Four Epimeric Tosylates of (5R)-2, 3-Epoxy-5-isopropenyl-cyclohexanol

Described is the synthesis of the four optically pure epoxy-tosylates 5, 6, 9 and 12, each with four chiral centers determined, from a single starting material, (R)(-) carvone.     

Synthesis of 2, 3-dideoxy-4-O-p-methoxybenzyl-L-erythro-hex-2-enono-1, 5-lactone

The synthesis of 2, 3-dideoxy-4-O-p-methoxy-benzyl-L-erythro-hex-2-enono-1, 5-lactone 9 from L-serine, using (1RS, 3S)-3, 4-isopropylidene-1-methoxy-1-phenylthio-butan-2-one 2 as key chiral intermediate, is described. Compound 9 is an interesting chiral precursor for the synthesis of L-sugars.     

Synthesis of (3-Ethoxycarbonyl But-3-en-2-yl)phenyl Sulfone and (2-Ethoxycarbonyl But-2-en-1-yl)phenyl Sulfone from Ethyl 2-Bromomethyl But-2-enoate

The synthetic usefullness of “acrylic” tin compounds has been largely demonstrated by BALDWIN and coworkers¹. We wanted to apply this methodology to prepare the peroxide precursors. Thus, we needed to synthesize (2-ethoxycarbonyl prop-2-enyl) phenyl sulfone 1, (2-ethoxycarbonyl but-2-en-1-yl) phenyl sulfone 2 and (3-ethoxycarbonyl but-3-en-2-yl) phenyl sulfone 3. We wish to report the synthesis of such compounds using the advantage of the complexing effect of Polyethyleneoxide 400 (PEO 400) on alkali cations. We also must to report the isomerisation of 2 to 3 in presence of traces of sodium sulfinate which make access to 2 difficult.     

Synthesis of the Dopamine Agonist (-)-Quinpirole

A convenient synthesis and resolution of (-)-trans-4aR,8aR-1-propyl-6-oxo-decahydroquinoline (4) is described. This compound is then converted into the D-2 selective dopamine agonist, (-)-quinpirole hydrochloride (3).     

Synthesis of Optically Active β-Halogeno-Phosphinates via Asymmetric Selection

Growing interest has been devoted in the last few years to the synthesis of optically active β-halogenoethyl sulphoxides¹ and sulphilimines² via chiral discrimination. In this context we have developed a synthesis of optically active isopropyl vinylphenylphosphinates 1 via kinetic resolution of isopropyl β-halogenoethylphenylphosphinates 2(a-c) by chiral bases (3–6) and we have studied the influence of the resolving agent and of the leaving group on the kinetic resolution.     

REACTION OF SCHIFF BASE OF THIOHYDRAZIDES WITH P(NR2)3

Abstract

Three pathways were observed in the reactions of Schiff bases of Thiohydrazides with P(NR₂)₃. (a) MeS-R₂N exchange: MeS-C([dbnd]S)-NHN[dbnd]CHPh (1) reacted with P(NR₂)₃ led to new Schiff bases, R₂N-C([dbnd]S)-NHN[dbnd]CH = Ph (2). (b) Cleavage of C[dbnd]S bond and the formation of P[dbnd]S bond: H₂N-C([dbnd]S)-NHN[dbnd]CH = Ph (3) reacted with P(NR₂)₃ gave rise to the thiophosphoric amide. (Et₂N)₂P([dbnd]S)-NH-CH = N-N[dbnd]CH-Ph (4). (c) Formation of thiadiazole and triazole: Schiff bases 2a and H₂N(MeS)C = N-N[dbnd]CH-Ph (6) reacted with P(NR₂)₃ respectively and produced 5-dimethylamino-2-phenyl-2,3-(2H)-1,3,4-thiadiazole (5) and 5-methylthio-2-phenyl-2,3-(2H)-1,3,4-triazole (7).     

An Efficient and Stereoselective Total Synthesis of (+/-)-Serricornine

An efficient and stereoselective total synthesis of (+/-)-serricornine (1) the sex pheromone produced by the female cigarette beetle Lasioderma serricorne F, is described. (3SR, 5SR, 6SR)-6-Ethyltetrahydro-3,5-dimethyl-2H-pyran-2-one (10) is prepared in 65% yield through lactonization of a 1:1 mixture of C-2 epimers of the corresponding esters.     

A new Method for the Synthesis of 5-Benzyl-1-(2-Hydroxyethoxy Methyl)Uracil (Bau), A Potent Uridine Phosphorylase Inhibitor,And Its N3-And N1, N3, -Substituted Analogs

A new methodology for the synthesis of 5-benzyl-l-(2-hydroxyethoxymethyl)uracil (BAU)² (1), a potent uridine phosphorylase inhibitor, has been developed. The coupling of bis(trimethylsilyl) derivative of 5-benzyl uracil with 2-acetoxyethoxymethyl bromide, followed by removal of the protecting 0-acetyl group, afforded compound 1. However, treatment of the silyl derivatives of 5-benzyluracil with 2-acetoxyethyl acetoxymethyl ether in the presence of stannic chloride as catalyst, followed by deblocking, gave three products,1, 2 and 3, respectively.     

Reductive Cleavage of 2-Acyl Tetrahydrofuranes. Synthesis of (Z)-6-Heneicosen-11-one,Pheromone of the Douglas Fir Tussock Moth

(Z)-6-heneicosen-11-one was prepared using the reductive cleavage of 2-tetrahydrofuryldecylketone 6 to 5-oxo-pentadecan-1-ol 7 as the key step of the synthesis.