127785-64-2

Usage

Uses

Used in Agricultural Industry:
Basifungin is used as a fungicide for controlling various fungal infections in crops due to its low concentration effectiveness and ability to inhibit fungal cell growth.
Used in Pharmaceutical Industry:
Basifungin is used as an orally available antibiotic for treating fungal infections in humans, as it can be ingested and still maintain its antimicrobial properties against yeast and other fungi.

Clinical Use

Aureobasidin A is a cyclic depsipeptide that is produced byfermentation in cultures of Aureobasidium pullulan.Aureobasidin A acts as a tight-binding noncompetitive inhibitorof the enzyme inositol phosphorylceramide synthase(IPC synthase), which is an essential enzyme for fungalsphingolipid biosynthesis. A unique structural feature of theaureobasidins is the N-methylation of four of seven amide nitrogenatoms. The lack of tautomerism dictated by N-methylationmay contribute to forming a stable solution conformerthat is shaped somewhat like an arrowhead, the presumed biologicallyactive conformation of aureobasidin-A.The pradimycins and benanomycins are naphthacenequinonesthat bind mannan in the presence of Ca2+ to disrupt the cell membrane in pathogenic fungi. Both demonstrate good in vitro and in vivo activity againstCandida spp. and C. neoformans clinical isolates.

InChI:InChI=1/C60H92N8O11/c1-17-38(9)46-57(75)65(14)47(36(5)6)52(70)61-42(32-35(3)4)55(73)67(16)50(60(11,12)78)59(77)79-49(39(10)18-2)58(76)66(15)48(37(7)8)53(71)62-43(33-40-26-21-19-22-27-40)54(72)64(13)45(34-41-28-23-20-24-29-41)56(74)68-31-25-30-44(68)51(69)63-46/h19-24,26-29,35-39,42-50,78H,17-18,25,30-34H2,1-16H3,(H,61,70)(H,62,71)(H,63,69)/t38-,39-,42+,43+,44+,45+,46-,47+,48+,49+,50-/m1/s1

Upstream product

• 93-10-7 quinoline-2-carboxylic acid 
• 137431-06-2 2-[3(S)-[(L-asparaginyl)-amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyl-decahydro(4aS,8aS)-isoquinoline-3(S)-carboxamide 
• 41844-71-7 methyl (S)-2-methoxycarbonylamino-3-phenyl-propionate 
• 128019-40-9 (3S,4aS,8aS)-N-tert-butyl-decahydroisoquinoline-3-carboxamide 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 1161-13-3 N-Cbz-L-Phe 
• 198020-19-8 (2R,2S)-(3S)-1,2-epoxy-3-phenylmethoxycarbonylamino-4-phenylbutane 
• 174602-81-4 (S)-2-[((2S,3R)-2-tert-Butoxycarbonylamino-3-methyl-pentanoyl)-methyl-amino]-3-methyl-butyric acid benzyl ester 
• 182205-65-8 (S)-2-{(S)-2-[((2S,3R)-2-Amino-3-methyl-pentanoyl)-methyl-amino]-3-methyl-butyrylamino}-4-methyl-pentanoic acid benzyl ester 
• 182205-76-1 (2R,3R)-2-[(S)-2-tert-Butoxycarbonylamino-3-(tert-butyl-dimethyl-silanyloxy)-3-methyl-butyryloxy]-3-methyl-pentanoic acid benzyl ester 
• 182205-77-2 (2R,3R)-2-[(S)-2-(tert-Butoxycarbonyl-methyl-amino)-3-(tert-butyl-dimethyl-silanyloxy)-3-methyl-butyryloxy]-3-methyl-pentanoic acid benzyl ester 
• 174602-83-6 (S)-2-[((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionyl)-methyl-amino]-3-phenyl-propionic acid benzyl ester 
• 182205-78-3 (S)-2-(tert-Butoxycarbonyl-methyl-amino)-3-(tert-butyl-dimethyl-silanyloxy)-3-methyl-butyric acid (1R,2R)-1-[((S)-1-benzyloxycarbonyl-2-methyl-propyl)-methyl-carbamoyl]-2-methyl-butyl ester 
• 174602-84-7 (S)-1-{(S)-2-[((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionyl)-methyl-amino]-3-phenyl-propionyl}-pyrrolidine-2-carboxylic acid benzyl ester 

Relevant academic research and scientific papers

Studies towards the synthesis of radiolabeled R106-1(LY295337)

A unique semisynthetic pathway has been used as a route to acquire radiolabeled material of a complex natural product, R106. The retro-aldol reaction of R106-1 gave a key intermediate R106-sarcosine that was used in a subsequent aldol reaction to incorporate acetone-[2-14C].

NOVEL POLYMORPHS OF SAQUINAVIR

The present invention provides novel polymorphs of saquinavir, processes for their preparation and pharmaceutical compositions comprising them. The present invention also provides a process for purification of saquinavir. The present invention further provides a novel process for preparation of known saquinavir crystalline form I.

NOVEL POLYMORPHS OF SAQUINAVIR

The present invention provides novel polymorphs of saquinavir, processes for their preparation and pharmaceutical compositions comprising them. The present invention also provides a process for purification of saquinavir. The present invention further provides a novel process for preparation of known saquinavir crystalline form I.

A PROCESS FOR THE PREPARATION OF SAQUINAVIR USING NOVEL INTERMEDIATE

The present invention provides a commercially viable process for preparing saquinavir and pharmaceutically acceptable acid addition salts thereof using novel intermediate. Thus, for example, N?2?-(2-quinolinylcarbonyl)-L-asparagine is reacted with pivaloyl chloride in methylene chloride in presence of triethyl amine to give pivaloyl N?2?-(2-quinolinylcarbonyl)-L-asparaginate, which is then condensed with [3S,4aS,8aS]-2-(3S-amino-2R-hydroxy-4-phenylbutyl)-N-(1,1-dimethylethyl)decahydro-3-isoquinoline carboxamide to give saquinavir, followed by treatment with methanesulfonic acid to give saquinavir mesylate.

Oral dosage forms of water insoluble drugs and methods of making the same

A method of making an oral dosage form of a water insoluble drug such as Saquinavir or Cyclosporine or Paclitaxel is carried out by: (a) providing a single phase working Solution comprising or consisting essentially of an active agent, water, a water-soluble polymer, and a solvent, said solvent selected from the group consisting of alcohol, acetone, and mixtures thereof; and may or may not contain a surfactant and pH of the said working solution may or may not be adjusted (b) providing particles formed from a pharmaceutically acceptable core material; (c) combining, preferably by spraying, said working solution with said particles to produce active agent-coated particles; such drug loaded particles may contain an external coat (d) drying said active agent-coated particles; and (e) forming said dried particles into an oral dosage form. Dried particles produced by the process, oral dosage forms containing such particles, and methods of treatment therewith are also described.

Total synthesis of an antifungal cyclic depsipeptide aureobasidin A

The first total synthesis of antifungal cyclic depsipeptide aureobasidin A is described. The synthesis was achieved mainly using bromotris(pyrrolidino)phosphonium hexafluorophosphate (PyBroP) as a coupling reagent. Peptide cyclization was carried out between L-allo-isoleucine (L-aIle1) and L-Pro9 residues in the linear nonapeptide at the final step of the synthesis. Synthesized aureobasidin A was completely identical with the natural antibiotic with respect to antifungal activity and physicochemical properties. Unusual reactions due to N-methylamino acid, an oxazoline-mediated reaction and an N, O-acyl migration, are also described.

Total synthesis of the antifungal cyclic depsipeptides Sch 57697 and aureobasidin A

A novel cyclic depsinonapeptide antifungal 1a (Sch 57697) and its isomer 1b were synthesized by a fragment coupling approach and this methodology was applied to the total synthesis of the natural product aureobasidin A. Synthetic strategies for coupling of N-methyl amino acids with minimal racemization are discussed. Biological evaluation of isomers 1a and 1b demonstrated the importance of chirality at the β-hydroxy-N-methylvaline (OHMeVal) position.

Synthesis of the HIV-proteinase inhibitor Saquinavir: A challenge for process research

The task of process research, namely developing efficient, economically and technically as well as ecologically feasible syntheses in time, is demonstrated on the HIV-proteinase inhibitor Saquinavir (1), a complex molecule comprising six stereo-centres. Based on the first 26-step research synthesis furnishing a 10% overall yield, process research established a new, short 11-step synthesis affording a 50% overall yield.

Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials.Six approaches for the large-scale synthesis of this compound have been studied.All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5.They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation.The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1.Kilogram quantities of Ro 31-8959 have been prepared using this route.

Total Synthesis of Aureobasidin A, an Antifungal Cyclic Depsipeptide

A total synthesis of an antifungal cyclic depsipeptide aureobasidin A was first achieved mainly using PyBroP as a coupling reagent.The synthetic cyclized product was completely identical with the natural antibiotic in all respects.Some unexpected reactions due to N-methylamino acid were also described.