A Simple and Efficient Procedure for the Synthesis of an Alendronate-Oligonucleotide Conjugate Via a Carbamate Linker

Abstract

Alendronate. an munobisphosphonate used clinically for thc treatment of osteoporosis and others bones deseases is a synthetic analog of pyrophosphate in which the labiie phosphoanhydride bond (HO)₂P(O)-O-P(O)(OH)₂ is replaced by a stable hydroxymethylene group (HO), P(O)-C(OH)R-P(O)(OH). The most important action of this bisphosphonate is the inhibition of the bone resorption. The mechanism of action is not completely elucided. One hypothesis is hat thc bisphosphonate act by suppressing osteoclast activity.[1] are used for the enzyme inhibition or for the antisens strategy parriculary in oncology The pharmacological interest of these two moieties encouraged us to bind a bisphosphonate at the 5′ OH of an oligonucleotide via a carbarnate bond. In the first time he synthesis conditions have been studied on model alcohol.     

Synthesis of Aminobisphosphonate

A new facile synthesis of aminobisphosphonate was reported. Dibenzylamine bisphosphonate (1) is prepared from dibenzylamine, triethyl orthoformate and diethyl phosphite. Deprotection by hydrogen transfer reaction and acid hydrolysis afforded aminobisphosphonate (2).     

Adsorption-Desorption Properties of Bisphosphonates

Abstract

Aminobisphosphonates have generated substantial interest recently for the treatment of bone diseases and as plant growth regulators, both alone and as a carrier for other drugs, because of the high affinity to the hydroxyapatite (HAP). We are investigating the drug delivery action of bisphosphonates for the treatment of osteoporosis and other bone diseases. Current studies include analysis of the adsorption-desorption processes of bisphosphonate drug carriers to bone mineral, as well as the design and synthesis of new bisphosphonate derivatives. The HAP adsorption data of aminomethylenebis-phosphonate (M P) (1). alendronate (2), and the prostaglandin derivative of bisphosphonate (PGE,-BP) (3) is shown on the graph.     

Synthesis of boranoate, selenoate, and thioate analogs of AZTp4A and Ap4A

We report efficient, one-flask procedures for the synthesis of a family of 14 analogs of AZTp₄A and Ap₄A containing BH₃, S, or Se, along with two bisphosphonate analogs of Ap₄A. These compounds should slow unwanted enzymatic hydrolysis and have the potential to create unique binding interactions in biochemical and structural studies of the excision reaction responsible for resistance of HIV-1 to AZT, as well as assist in drug design.     

Synthesis of New Tetraethyl(N-alkyl-1-aminoethan-1,1-diyl)bisphosphona-tes and ESR Analysis of Chemical Exchange of Derived Nitroxides of Acyclic Aminobisphosphonates

The synthesis and the full characterization of two new linear bisphosphonates (tetraethyl(N-tert-butyl-1-aminoethan-1,1-diyl)bisphosphonate and tetraethyl(N-sec-butyl-1-aminoethan-1,1-diyl)bisphosphonate), and the first analysis of the ESR spectra of the corresponding nitroxides is reported. The preliminary results of theoretical calculations on model compounds suggest a small B₀ (in the McConnell equation). The results of bisphosphonate ester and bisphosphonic acid are similar. The discrepancies of P coupling for the diphosphorus compound stems from B₂ that is different when the dihedral angle is larger than 90°.     

Formation of TTF Derivatives VIA the Phosphonate Way: A Mechanistic Study Leading to an Improved Procedure

Abstract

Until now, the only effcient method¹ for the selective preparation of unsymmetrically substituted tetrathiafulvalenes (TTF), precursors of organic conductor materials, has been the condensation of an α-metalated phosphonate with an iminium salt. The major limitations of this method are the low yields (0–50%). Our gól was to investigate the mechanism of this reaction in order to improve thc yields.     

Dodecanoyl thiosemicarbazide derivatives as useful synthons in the synthesis of 1,2,4-triazole, 1,3,4-thiadiazole,and 1,3-benzothiazole derivatives

A convenient synthesis of the dodecanoyl thiosemicarbazide derivatives 3a, b has been achieved from the reaction of 2-benzamido-3-arylacryloylhydrazides 1a, b and lauroyl isothiocyanate (2). The thiosemicarbazide derivative 3a is used as precursor for synthesis of 1,2,4-triazole, 1,3,4-thiadiazole, and 1,3-benzothiazole derivatives. The antimicrobial activity of some of the synthesized compounds was tested.     

Synthesis of new semi-rigid chelating agents for samarium-153

This study describes a simple, efficient synthesis pathway from trans-1,2-diaminocyclohexane that provides access to a new class of semi-rigid polyamine, polycarboxylic, and polyphosphonic ligands. The key steps in synthesis were the functionalisation (with an appropriate branching group) of a bisphosphonate diaminocyclohexane derivative and the introduction of methanephosphonic functions by a rarely used method.     

New and Practical Synthesis of Montelukast Sodium,an Antiasthmatic Drug

Abstract

A new and practical synthesis of montelukast sodium, an antiasthmatic drug, is described. The key steps are the synthesis of nitrile derivative 4 by chiral reduction of keto ester 9 using (?)-DIP-Cl, synthesis of vinylquinoline framework 16 by Wittig reaction, and Heck coupling of nitrile 4 with vinylquinoline 16. The method is operationally simple and suitable for the industrial production of the drug substance.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

A stereoselective palladium-catalyzed synthesis of amino alkenyl geminal bisphosphonates

The synthesis of amino alkenyl geminal bisphosphonates is carried out via the palladium-catalyzed ring opening of tetraethyl 2-vinyl-1,1-cyclopropane bisphosphonate 1 in the presence of a secondary amine at room temperature. The reaction proceeds with complete regio- and stereoselectivity.     

Isocamphanyl-γ-butyrolacton,ein neuer Sandelholzriechstoff

The synthesis of a new compound with a sanddalwood odour is described. The synthesis of the lactone1 has been designed by molecular considerations: a bicyclus with a side chain containing 5–7 carbon atoms and an oxygene containing osmophoric group. One route to synthesize1 leads from the ketone3 via theMannich base4 to the -ketonitrile6 which after hydrolysis to the -keto acid7 and reduction of the latter cyclises spontaneously to1. A shorter route starts from the -bromoketone13 which could be transformed by malonic ester synthesis into7. Other synthetic routes, e.g. cyanoethylation to the homologous -lactone16 aldol condensation, alkylation, carboxymethylation and carboxyethylation of3 failed as well as the preparation of the oxazoline protected 3-bromopropionic acid for aGrignard synthesis with3. 1 exhibits a sweet, warm odour, of sandalwood with an interesting note of cedarwood.

Teil der Diplomarbeit vonSchindler, K., Universität Wien, 1979.     

Synthesis of (+)-(3R,5R)-3-Hydroxy-5-decanolide and Massoialactone,and Formal Synthesis of Verbalactone

Total synthesis of (3R, 5R)-(+)-3-hydroxy-5-decanolide (1) and massoialactone (2), and formal synthesis of verbalactone (3), have been reported.     

Preparation of N,N-Bis[2-[N',N'-Bis[(Tert-Butoxycarbonyl)Methyl]-Amino]Ethyl-L-Aspartic Acid: An Intermediate in the Synthesis of MRI Contrast Agents

A preparation of DTPA carboxylic acid 1, a suitable intermediate in the synthesis of MRI contrast agents 2, is described starting from α-tert-butyl-β-benzyl-L-aspartate hydrochloride. In addition, an alternative procedure for the synthesis of bromide 3b is presented.     

Candidate Trail Attractants of Reticultermes lucifugus: Stereoselective Syntheses of (3Z, 6E,BE)-(3Z, 6E, 8Z)-and (3Z, 6Z, 8Z)-3,6,8 -Dodecatrien-1-OL1

Stereoselective syntheses on a gram scale of (3Z,6E,8E)-, (3Z,6E,8Z)-and (3Z,6Z,8Z)-3,6,8-dodecatrien-1-ol, 8, 9 and 10, respectively, are described. A key step of the synthesis of 8 consisted of a copper-mediated coupling reaction between 4-(2-tetrahydropyranyloxy)-1-butynylmagnesium bromide (15) and the mesyl ester of (2E,4E)-2,4-octadien-1-ol (14). A similar copper-mediated reaction between 15 and the mesyl ester of (E)-2-octen-4-yn-1-ol (19) was used to construct the C-12 carbon skeleton of 9. On the other hand, the synthesis of 10 was based on a palladium-promoted reaction between (Z)-1-bromo-1-pentene (23) and the organozinc bromide derived from 3,6-heptadiyn-1-yl acetate (27).     

Determination of some antioxidants by derivative spectrophotometric method and high-performance liquid chromatography

Abstract

The UV-derivative spectrophotometric method was used for assaying butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) in pure state and in laboratory mixtures. Ir; this paper the results are presented using zero-crdssing technique. In this way, thc interference of two components mixed together has been eliminated. That is the greatest advantage of derivative spectroscopy compared with the classical UV-spectrophotometric method. After analysing the criteria f o r the application of this method, the amounts of these substances were determined. Simul taneously, a highperformance liquid chromatography was used.     

Synthesis and Antimicrobial Properties of New Thiosemicarbazide, 1,2,4-Triazole,and 1,3,4-Thiadiazole Derivatives of Sulfanylacetic Acid

Abstract

1,2,4-triazole and 1,3,4-thiadiazole derivatives are still considered a viable lead structure for the synthesis of more efficient antimicrobial agents having a broad spectrum of activity. This study presents the synthesis and antimicrobial evaluation of a new series of substituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives. Reaction of 4-phenyl-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thione with ethyl bromoacetate yields the corresponding ethyl acetate (1). In the subsequent reaction with 100% hydrazine hydrate, the hydrazide (2) was obtained, which was converted with isothiocyanates to new acyl derivatives of thiosemicarbazide (3a–l). The cyclization of these compounds in alkaline media resulted in the formation of new derivatives of 1,2,4-triazole (4a–i), whereas in acidic media new derivatives of 1,3,4-thiadiazole (5a,b,g) were obtained. All synthesized compounds were screened for their in vitro antimicrobial activities.     

Linear Synthesis of The Methyl Glycosides of Tri-, Tetra-, and Pentasaccharide Fragments of The Shigella Flexneri Serotype 5A O-Antigen

ABSTRACT

The stepwise synthesis of methyl α-D-glucopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranoside (EBC-OMe, 1), methyl α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranoside (A(E)BC-OMe, 2), and methyl 2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranoside (DA(E)BC-OMe, 3) is described. Compounds 1, 2 and 3 constitute the methyl glycosides of fragments of the O-specific polysaccharide of Shigella flexneri serotype 5a. Methyl 2,4-di-O-benzoyl-α-L-rhamnopyranosyl-(1→3)-2,4-di-O-benzoyl-α-L-rhamnopyranoside was an appropriate BC precursor for the synthesis of 1. For the synthesis of the branched targets 2 and 3, a benzyl group was best suited at position 2 of rhamnose C. Thus, methyl 4-O-benzyl-α-L-rhamnopyranosyl-(1→3)-2,4-di-O-benzyl-α-L-rhamnopyranoside was the key intermediate to the BC portion. In all cases, 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride was a convenient E precursor, when used in combination with titanium tetrafluoride. All along, attention was paid to steric hindrance as a factor of major impact on the condensation steps outcome. Therefore, based on previous experience, 2-O-acetyl-3,4-di-O-allyl-α-L-rhamnopyranosyl trichloroacetimidate and 3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-α-D-glucopyranosyl trichloroacetimidate were used as donors. Both suited all requirements when used as key precursors for residues A and D in the synthesis of 3, respectively.     

Systematic approach to the chemical synthesis of arabidopyrones,the unique α-pyrones of Arabidopsis metabolites

Abstract

Total synthesis of two arabidopyrones, iso-arabidopyl alcohol (1) and iso-arabidopic acid (2) isolated from Arabidopsis thaliana was achieved for the first time using Claisen condensation and Wittig reaction as the key steps. In addition, arabidopic acid (4) was synthesized from the methyl ester of arabidopyl alcohol (3). Thus, chemical synthesis of the unique natural α-pyrones 1–4 was accomplished with a short synthetic route by a systematic approach from readily available substances.     

A Short,Efficient Synthesis of the Octamannan Residue of High Mannose Type Sugar Chains

Abstract

An efficient route for the synthesis of octamannan 1, found in high mannose type sugar chains, is described. to construct octasaccharide 1 by as few synthetic steps as possible, we employed a chemoenzymatic strategy: the enzymatic synthesis of oligosaccharide blocks using glycosidases followed by chemical coupling to form a branched structure. By use of this methodology, many synthetic steps were eliminated and 1 was easily synthesized.