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.

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Heterocyclisch anellierte Pyrazin-1,4-dioxide; 1. Mitt.: Die positionsselektive Synthese von Pyrido[2,3-b]pyrazin-1,4-dioxiden

The positionsselective synthesis of the title compounds5 is described and the structure established by reduction of5c to8 and synthesis of the latter by an unambiguous method.

     

Stereoselective Synthesis of Diaminosuberic Acid Via a Chiral Alkynyl Oxazolidine

A novel, stereoselective synthesis of enantiomerically pure, N-protected diaminosuberic acid (6) is presented. The key step in the synthesis is the oxidative dimerization of the chiral alkynyl oxazolidine (2).     

Stereoselective total synthesis of paecilomycin E and F and its two congeners Cochliomycin C and 6-epi-Cochliomycin C

An efficient and concise approach to the total synthesis of Paecilomycins E (1) and F (2), Cochliomycin C (4) and 6-epi-Cochliomycin C (3) is described. The synthesis involves novel route to the synthesis of Paecilomycin E and F and further conversion to Cochliomycin C and 6-epi-Cochliomycin C. Olefin metathesis and base promoted macro lactonization being the key reactions followed by chlorination to achieve target Cochliomycin C and 6-epi-Cochliomycin C.     

A Synthesis of Two Novel Benzo[f]ninhydrin Analogs: 6-Methoxybenzo[f]ninhydrin and Thieno[f]ninhydrin

Improved methodology for the synthesis of benzo[f]ninhydrin (1) is described. The generality of this approach is illustrated with the synthesis of two novel analogs, 6-methoxybenzo[f]ninhydrin (3) and thieno[f]ninhydrin (4).     

Transformation of Glucose into a Novel Carbasugar Amino Acid Dipeptide Isostere

The synthesis of a novel carbasugar amino acid (15), starting from D‐glucose and using the Ferrier rearrangement as a key step, is reported. Compound 15 is implemented as dipeptide isostere in the synthesis of a Leu‐enkephalin analog.     

A Novel Synthesis of 3,4-Discubstituted-1H-pyrazolo[3,4-b]quinolines

A simple and efficient synthesis of pyrazolo[3,4-b] quinolines is described. The synthesis involves reaction of 2-amino-3-cyanoquinoline-4-carboxylates(1) with hydrazine hydrate to give regioselectively only pyrazolo[3,4-b]quinolines (2). No formation of pyridazino quinolines (3) is observed.     

An improved synthesis of ‘octa-acid’ deep-cavity cavitand

An improved synthesis of a water-soluble deep-cavity cavitand (octa-acid, 1) is presented. Previously (Gibb, C.L.D.; Gibb, B.C. J. Am. Chem. Soc. 2004, 126, 11408–11409), we documented access to host 1 in eight (non-linear) steps starting from resorcinol; a synthesis that required four steps involving chromatographic purification. Here, we reveal a modified synthesis of host 1. Consisting of seven (non-linear) steps, this new synthesis involves only one chromatographic step, and avoids a minor impurity observed in the original approach. This improved synthesis is therefore useful for the laboratories that are investigating the properties of these types of host.     

Attempted Synthesis of Tricyclo[3.3.2.024]DEC-2(4)-ENE

The synthesis of tricyclo[3.3.2.0^2,4]-dec-2(4)-ene (3) has been attempted using a route analogous to those previously developed for 1 and 2. Complications were encountered in the synthesis. The conformational problems of the larger polycyclic structures in the synthesis of 3 must be more difficult to overcome than the increased angle strain of the smaller rings when 1 or 2 are synthesized.     

A New Synthesis of 3-Alkyl Isoxazoles

A two step facile synthesis of isoxazoles is described. The synthesis involves copper catalysed bromoform addition to an alkene (1) to afford tribromo derivative (2) which on treatment with sodiumnitrite in DMF gives the corresponding isoxazole (3).     

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 Eupolauridine and Its Benzo-Annulated Derivative

The unique diazafluoranthene alkaloid eupolauridine (1) was synthesized by a three-step route utilizing as the initial step the thermal rearrangement of the oxime O-crotyl ether 12, which afforded onychine (2). Bracher pyridine synthesis procedure subsequently converted 2 into 1. On the other hand, Friedländer reaction was employed for the synthesis of 3, which is a benzo-annulated derivative of eupolauridine (1).     

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.     

An Improved Asymmetric Synthesis of Unusual Amino Acid (2S,3S)‐3‐Hydroxyproline

Abstract

An improved three‐steps method for the conversion of N‐benzyl (S)‐3‐hydroxypyrrolidin‐2‐one 6 to (2S,3S)‐3‐hydroxyproline 1 is reported. The key step is the reductive cyanation of 6. The synthesis of 1 constitutes a formal asymmetric synthesis of (2S,3S)‐3‐hydroxyproline betaines 2.     

1-Norbornyllithium as a Precursor for the Synthesis of Novel Organic 1-Bicyclo[2.2.1]Heptane Derivatives and for the Improved Preparation of 1-Chloro-Bicyclo[2.2.2]octane

An improved strategy for synthesis of 1-chloro-bicyclo[2.2.2]octane is described in which the key compounds 1-norborny substituted ethyl formate(3) or 1-norbornylcarbaldehyde (7) were prepared from 1-norbornyllithium(1). The latter appeared as a useful precursor for the synthesis of various organic bridgehead substituted derivatives.     

A Facile Synthesis of the Pyranonaphthazarin System

The synthesis of pyranoquinone 9 starting from hydroxyquinone 4 through Michael adduct 5 is described.     

Efficient Synthesis of 2‐Aminothiazole‐4‐phenyl‐5‐acetamides via the Open Chain Tautomers of γ‐Keto Amides

A simple and efficient method is described for the synthesis of new functionalized 2‐aminothiazoles, the 2‐aminothiazole‐4‐phenyl‐5‐acetamides 5, in 67–96% yields based on an application of the Hantzsch synthesis. The method involves the reaction of thiourea with 3‐benzoyl‐3‐bromo‐propionamides 4 prepared from the corresponding 3‐benzoylpropionamides 3. The tautomeric structure of the γ‐keto amides 3 and 6 is directly related to the present study, because 2‐aminothiazoles 5 are readily obtained from the corresponding open chain γ‐keto amides 3.     

A New Approach to the Ribosylribitol Intermediate for the Synthesis of Haemophilus Influenzae Type B Oligosaccharides

Abstract

The 3-o-allyl-2,5-di-o-benzoyl-β-d-ribofuranosyl trichloroacetimidate 9 was obtained in good yield after eleven steps from glucose. This imidate has proved to be an excellent precursor for the synthesis of ribosylribitol 13, which is the key monomer unit for the synthesis of Haemophilus influenzae type b PRP oligosaccharides.     

Studies on Flavans. III. The Total Synthesis of (±)-7,4′-Dihydroxy-3′-methoxyflavan, (±)-7,3′-Dihydroxy-4′-methoxyflavan,and (±)-7,4′-Dihydroxyflavan

Abstract

The first total synthesis of (±)-7,3′-dihydroxy-4′-methoxyflavan (1) and (±)-7,4′-dihydroxy-3′-methoxyflavan (2), along with the synthesis of (±)-7,4′-dihydroxyflavan (3), three naturally occurring flavans, were described. The key step is the cyclization of 1,3-diaryl-1-propanol by BF₃·Et₂O.     

A Short,Efficient Synthesis of 6-Cyano-1-tetralones

A new, short and high-yield synthesis of 6-cyano-1-tetralones is described. Triflate intermediates 8 and 9 are versatile intermediates for the synthesis of other 6-substituted tetralones.