MOLECULAR AMD CRYSTAL STRUCTURES OF LIPIDS AND RELATED COMPOUNDS

Molecular-level structures of lipids and related organic long-chain compounds were investigated by means of vibrational spectroscopic and X-ray diffraction methods. Various spectroscopic techniques applicable to structural studies of lipid systems were developed. Various types of solid-state phase transformations were found in even- and odd-numbered saturated fatty acids and their molecular mechanisms were considered. Crystal structures of some modifications of a series of cis-mono-unsaturated fatty acids were determined by the three-dimensional X-ray analysis and new types of molecular conformation as well as of subcell arrangement of the cis-mono-unsaturated acyl chains were found. An order-disorder type phase transformation accompanied with a partial melting at the interface of the molecular layers was found in some modifications of cis-mono-unsaturated fatty acids. Molecular conformations and crystal structures of the polymorphs of methyl oleate and triglycerides containing an oleoyl chain at the 2-position were investigated on the basis of the spectroscopic data.     

1,2- and 1,3-diphosphetanes from alkylidenephosphines

Abstract

Alkyl- or arylbis(trimethylsilyl)phosphines as well as tris(trimethylsilyl)phosphine and the corresponding arsines react with acyl chlorides to give [1-(trimethylsiloxy)alkylidene]phosphines 1 and -arsines 2; most of their 2,2-dimethylpropylidene derivatives are thermally stable at room temperature. With the same class of phosphines as starting compounds and carbon disulfide [bis(trimethylsilylsulfano)methylidene]phosphines 3 are formed, whereas [(dialkylamino)methylidene]-4 and [diarylmethylidene]phosphines 5 or the corresponding arsines 6 and 7 can be obtained from acyl amides or ketones.¹     

Hydrogen bonded phosphate structures

Abstract

Some phosphate esters form structures containing infinite chains of hydrogen bonded units, others form discrete dimeric units, and still others form columns or chains of dimeric units. We have formed unique hydrogen bonded phosphorus ester systems which incorporate catechol molecules of crystallization, [HOC₆H₄OP(Ph)O₂][PPh₄]· catechol, 1, and [HOC₆H₄OP(Ph)O₂] [C₅H₅NH]· catechol, 2. X-ray analysis shows a chain arrangement in 1 and dimeric phosphonate units in a chain structure for 2 By comparing our results with literature examples, a classification of hydrogen bonding in phosphates results which proves useful in interpreting orientational influences at enzyme active sites.     

An Improved Method for the Synthesis of 3.6-Di-O-Methyl-D-Glucose: Preparation of the Neo-Glycoprotein Containing 3,6-Di-O-Methyl-β-D-Glucopyranosyl-Groups

Abstract

3,6-Di-O-methyl-D-glucose, the non-reducing terminal sugar of the phenolic glycolipid-I, elaborated by Mycobacterium leprae, has been synthesized by a simple procedure and in high yield. 3-O-Methyl-D-glucose was converted to the corresponding benzyl glycoside and then tosylated to give benzyl 3-O-methyl-6-O-tosyl-β-D-glucopyranoside. Displacement of tosyl group with sodium methoxide followed by debenzylation afforded 3,6-di-O-methyl-D-glucose in high yield. Condensation of the acetobromo derivative of 3,6-di-O-methyl-D-glucose with 8-ethoxycarbonyloctanol gave 8-ethoxycarbonyloctyl 2,4-di-O-acety 1–3, 6-di-O-methy 1-β-D-glucopyranoside. This was then deacetylated, converted to hydrazide, and finally coupled to bovine serum albumin via the acyl azide intermediate. The neo-glycoprotein containing the 3,6-di-O-methyl-β-D-glucopyranosyl group is useful for serodiagnosis of leprosy.     

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.     

CRYSTALLIZATION PHENOMENA IN FATS AND LIPIDS

This article reviews recent studies of crystallization behavior of polymorphic modifications of principal saturated and mono-cis-un-saturated fatty acids, and of mixed-acid triacylglycerols; stearic acid, oleic acid, erucic acid and SOS (symmetric l,3-di-stearoyl-2-oleoyl glycerol). Thermodynamic and kinetic aspects of the polymorphic crystallization are discussed in relation to molecular structures and thermal properties, which have newly been elucidated with X-ray diffractometry and vibrational spectroscopy.     

Hydroxyphosphoranes tautomers of γ hydroxylated phosphoric esters - structure and acidity

Abstract

The crystal structure of the triethylammonium salts of hydroxyphosphoranes 1a and 2 was resolved by X Ray diffraction. The first one has a TBP geometry slightly deformed with the phosphorus atom at the center, and the second one is a polycylic dimer containing two TBP which present the same deformations. In both cases, the P-O^? bond lengths are short and dioxaphospholane rings planar. These two particular properties can be related to the strong Bronsted acidity of compounds 1a and 2. Effectively, the pKa of hydroxyphosphoranes 1a, 1b and 2, determined by potentiometrical titration in DMF or DMSO solutions are characteristic of strong acids.     

t-Butyldiphenylsilyl-Lithium and Lithium Bis(t-Butyldiphenylsilyl)Cuprate. New Silylating Reagents

t-Butyldiphenylsilyl-lithium reacts with carbonyl derivatives to give α -hydroxysilanes in high yields. Lithium bis (t-butyldiphenylsilyl)cuprate reacts with α, β-unsaturated ketones and esters and with acyl chlorides to give β-silylcarbonyl1 compounds and acylsilanes. β-t-Butyldiphenylsilylketones are masked α, β-unsaturated ketones.     

The Effect of Substituents on the Reactivity of the Double Bond of D-Glycals

Abstract

A study was made concerning the effect of substituants at 0-3, 0-4 and 0-6 of d-galactal and d-glucal (1, 5-anhydro-2-deoxy-d-lyxo- and -d-arabino-hex-1-enitol, respectively) on the double bond reactivity in the chloroazide addition reaction. Results from the quantum chemical calculations of the model structures (ab initio) and also of the whole cyclic molecules in the half-chair conformation (MINDO-3) together with the reaction indices of olefin carbon atoms are presented. These studies snow that (1) the double bond reactivity and the chloroazide addition mechanism are only affected by the substituent at 0-3; (2) the influence of the acyl group is only due to its inductive effect; (3) no interaction between the acyl and the olefin fragments through space was detected. Three 0-acetyl-di-0-benzyl-d-galactals were synthesized.     

A Remarkable Synthesis of the Bicyclo[4.2.1]Nonenedione System

Allylation of the C-2 enolate of the bicyclo[3.3.1]nonenedione 1 proceeds with an unusual acyl migration to yield the C-allyl ester 5 of the rearranged bicyclo[4.2.1]nonenedione system.     

A General Method for Stepwise Elongation of the (1→5)-α-D-Arabinofuranan Chain

Condensation reaction of 3,5-di-O-benzoyl-1,2-O-(1-cyanoben-zylidene)-β-D-arabinofuranose (2) with benzyl and allyl 2,3-di-O-benzoyl-5-O-triphenylmethyl-α-L-arabinofuranosides (5a and 5b) in methylene chloride in the presence of triphenylcarbenium tetrafluoroborate as catalyst under high vacuum gave α-(1→5)-linked dimeric D-arabinofuranoside derivatives (6a and 6b). One of the dimeric compounds (6a) was debenzoylated, triphenylmethylated, and rebenzoylated to give a dimeric homolog of 5a (8). Similarly for the preparation of 6a, 8 was condensed with 2 to provide an α-(1→5)-linked trimeric D-arabinofuranoside derivative (9). Further elongation of the glycoside chain might be possible in the same way.     

Syntheses of Methyl 2,3-di-O-Glycyl-α-D-glucopyranoside and 4,6-di-O-Glycyl-2,3-di-O-methyl-α-D-glucopyranoside,and Removal of Aminoacyl Groups from Sugar Moieties

Abstract

To confirm the potential usefulness of amino acid residues as protecting groups for sugar hydroxyls, methyl 2,3-di-O-glycyl-α-D-glucopyranoside (5) and methyl 4,6-di-O-glycyl-2,3-di-O-methyl-α-D-gluco-pyranoside (7) were synthesized as reference compounds. Conditions were then established for the removal of these aminoacyl groups from the sugar molecules. The reference compounds were easily prepared by condensation of methyl α-D-glucopyranoside derivatives with N-protected glycine in the presence of dicyclohexyl-carbodiimide (DCC). The aminoacyl groups were removed by alkaline treatment, as were conventional acyl groups and also with ease by enzymatic hydrolysis using Pronase E. Conventional ester and ether protecting groups are not removed by such enzymatic treatment. Removal of aminoacyl group from sugar moieties on a practical scale is also described.     

Countercurrent Chromatographic Separation of Bacteria with Known Differences in Surface Lipopolysaccharide

Abstract

Countercurrent chromatography was used to separate cells of Salmonella typhimurium whose surfaces were identical except for the proportion of lipopolysaccharide molecules with long versus short chain polysaccharide chains. Large differences in partition properties resulted from slight differences in polysaccharide composition, and the results suggest that the physical state of the molecules, as well as their composition, can affect the partition of such cells.     

Synthesis of the Pheromones, (E)-3, 7-Dimethyl-2, 7-Octadienyl Propionate, (E)-3, 7-Dimethyl-2-Octene-1, 8-Diol and Frontalin from a Common Intermediate1

Ketal ester 9 has been prepared in five steps from methyl levulinate 4 (scheme 1). The propionate 1, diol 2 and (±) frontalin 3 were prepared from ester 9 employing the routes shown in scheme 2,3 and 4 respectively. The branched chain alkenes 13 and 20 were prepared conveniently from the primary alcohols 11 and 10 following the procedure of S.Wolff. Triethyl phosphonopropionate 7 has been prepared by methylating triethylphosphonoacetate with methyl iodide in the presence of sodium hydride.     

A Total Synthesis of (±)-Trichodiene

Trichodiene (1), a sesquiterpene hydrocarbon, was isolated from the extract of mycelium of Trichothecium roseum. The structure of trichodiene (1) was elucidated by Nozoe and Machida in 1970 via degradation and spectroscopy.¹ Trichodiene (1) has been shown to be the biogenetic precursor of the trichothecane family of sesquiterpenoids as characterized by the cytotoxic fungal metabolite (-)-trichodermin (2).^2,3 The structure and absolute stereochemistry of (-)-trichodermin (2) were determined by X-ray diffraction and, therefore, the structure and absolute stereochemistry of trichodiene (1) are now firmly established.⁴ We wish to report a total synthesis of (±)-trichodiene (1) via previously reported lactone 3.^5,6     

REACTIONS OF DITHIOLETHIONES WITH N,N-DICHLOROAMIDES

Abstract

Dependent on the starting materials and the reaction conditions N,N-dichloroamides Cl₂N-X (X = COaryl, CO₂alkyl, SO₂aryl, SO₂N(alkyl)₂) react with dithiolethiones 1 and 5 to N-(dithiolyliden)amides 2, 6, S-(dithiolylidene)sulfimides 3, thionoxides 7 and dithiolones 4, 8. The mechanisms have been studied.     

The Reaction of N-Phenyliminoketenylidenetriphenyl-phosphorane with α,β-Unsaturated Carbonyl Compounds. Synthesis of New Pyran Derivatives

Abstract

The reaction of N-phenyliminoketenylidenetriphenylphosphorane [a] (1), with 2-benzylidene-1, 3-indandione (2), 1,2-diphenyl-3,4-pyrazolidenedione (3)and/or 5-benzylidene barbituric acid (4) has been investigated. When ylide 1 was allowed to react with compounds 2, 3 or 4 in THF at ambient temp. the corresponding new pyrano-phosphoranylidenes 5, 6 or 7 were obtained. The elemental microanalyses, IR, ¹H NMR, ³¹P NMR and MS data agree with the structure of the cyclic iminophosphoranes by [4+2]-cycloaddition and exclude 4-membered ring structure by [2+2]-cycloaddition. When the Wittig reaction was carried on the pyrano-phosphoranes 5, 6 or 7 using p-nitrobenzaldehyde, the exocyclic olefins together with triphenylphosphine oxide were isolated.     

Darstellung Der Isomeren 1,6-DI-O-Acetyl-3,4-Didesoxy-α, β-D-Glycero-Hex-3-Enopyrahos-2-Ulosen

Abstract

Prolonged treatment of tetra-O-acetyl-1, 5-anhydro-hex-1-enitols (“tetra-O-acetyl-hydroxy-glycals”) 3 and 5 with BF₃ in CH₂Cl₂ at RT lead to anomeric mixtures of the title compounds 2 and 4a, the α-anomer 4a dominating. Reaction of 5 gave the higher yields of 4a (71%) and 2 (12%), the results being accounted mechanistic grounds. The same reaction performed in an aromatic solvent, like toluene, gave rise to competing C-alkylation., The ortho and para-tolyl derivatives 6 and 7, also with enone structure, were isolated in a combined maximum yield of 40% from 5. β-Enone 2 was also prepared in moderate yield by thermolysis of β-d-glucopyranose pentaacetate (1). In this case no α-anomer 4a was detected.     

The Reaction of Methyl 3-O-Benzyl-4, 6-O-benzylidene-α-D-mannopyranqside with Diethylaminosulfur Trifluoride (DAST)

Methyl 3-O-benzyl-4, 6-O-benzylidene-α-D-mannopyranoside (2), when treated in diglyme at 1000[ddot] with DAST, undergoes a rapid reaction involving the participation of the axial methoxyl group at C-1 to give 3-O-benzyl-4, 6-O-benzylidene-2-O-methyl-α- (4) and β-D-gluco-pyranosyl fluoride (3), isolated in a combined yield of 75-80%. In the presence of pyricfine and at room temperature, the major product formed is methyl 3-O-benzyl-4, 6-O-benzylidene-2-deoxy-α-D-eiythro-hex-2-enopyranoside (11). The structures 3, 4 and 11 have been confirmed by analysis of their NMR spectral data, as well as by chemical transformations into compounds of established structure.     

An Entry to the Optically Pure β-Lactam Skeleton Based on 1,3-Dipolar Cycloaddition of Nitrones to 4,6-Di-O-Acetyl-2,3-Dideoxy-D-Threo-Hex-2-Enono-1,5-Lactone

Abstract

Saturated lactone 8, easily available by 1,3-dipolar cycloaddition of nitrone 4 to unsaturated lactone 7 was transformed into the β-lactam 22having a polyol side chain at the C-3 position of the azetidinone ring. The same sequence of reactions, when applied to 9 and 10 failed to give the respective β-lactams owing to the removal of the nitrogen atoms from those molecules.