Total synthesis of antibiotic A23187 (calcimycin) from D-glucose

The fully stereocontrolled synthesis of A23187 by using the chirons derived from D-glucose is described.     

Total Synthesis of Antitumor Antibiotic Derhodinosylurdamycin A

The first total synthesis of derhodinosylurdamycin A, an angucycline antitumor antibiotic, has been described. The synthesis features a Hauser annulation followed by pinacol coupling to construct the tetracyclic angular aglycon, a Stille coupling of glycal stannane and tetracyclic aryliodide followed by stereoselective reduction to afford the 2‐deoxy β‐C‐arylglycoside, and a late‐stage stereoselective glycosylation for the preparation of derhodinosylurdamycin A. This synthetic strategy should be amenable to the chemical synthesis of analogs of derhodinosylurdamycin A bearing diverse 2‐deoxy sugar subunits for structure and activity relationship studies.     

Synthesis of (2S,4S)-4-Hydroxyproline from D-Glucose

Diacetone-D-glucose 1 gives 3- O -methylxanthate 2 on reaction with NaH/Me I. Reductive deoxygenation of compound 2 by Bu₃SnH gives the corresponding 3-deoxy glucose derivative 3 and on acid-catalyzed regioselective deprotection of C-5,6-acetonide gives the diol 4. The diol on oxidative cleavage with NaIO₄ gives the aldehyde 5, which on further condensation with benzylamine followed by reduction with NaBH₄ gives the amine 7. Z-Protection of the amine followed by methanolysis gives methyl furanoside 9. Reaction of 9 with methanesulfonyl chloride/Et₃N gives the corresponding C-3-O-mesylate derivative 10. Catalytic hydrogenation of compound 10 (Pd/C/H₂/MeOH 3 kg) gives bicyclic oxaazo compound 11, due to deprotection of the N-benzyl- and Z-protecting groups and intramolecular nucleophilic displacement of the C-2- O-mesylate by the C-5 amine in a one-pot reaction. Z-Protection of the amine 11 followed by acid-catalyzed hydrolysis gives acetal 13. Reduction of acetal by use of NaBH₄ gives Z-prolinol 14. Selective oxidation of diol 14 by (2,2,6,6-tetramethylpiperidin-1-yl)-oxyl (TEMPO)/[(bis)(acetoxy)iodo]benzene (BAIB) and NaClO₂/NaH₂PO₄, followed by Z-deprotection, gives the title compound I in 3.5% overall yield from D-glucose.     

Total Synthesis of (±)-Calanolide A

The total synthesis of (±)-Calanolide A, incorporating a ring-forming sequence different from previous procedures, is described.     

Total Synthesis of (±)-Celaphanol A

Celaphanol A was a diterpene isolated from the stems of Celastrus stephanotifolius1, which have been the subject of continued and growing interest, due to the range of biological activities shown by many members of this family2. Some have been used in traditional medicine3 or as a stimulant4 from ancient times. In order to further study the relationship between the structure and biological activity of the diterpene compound and as an extension of diterpenoid synthesis in our laboratory5, 6, …     

Total Synthesis of (-)-Muscoride A

The recently isolated cyanobacterium metabolite muscoride A was synthesized in 15 steps and in 4.3% overall yield. Novel structural features of this peptide antibiotic include the presence of a threonine-derived bioxazole core and an N-(1,1-dimethyl)allyl ("reverse prenyl") valine residue. In the context of our synthesis, efficient new strategies for the preparation of these segments were developed. The synthesis of two epimers of muscoride A allowed the unambiguous assignment of the relative and absolute configuration of the natural product by NMR and optical rotation analyses.     

Synthesis of a Chiral Hexane-1,6-Dinitrile from D-Glucose

Abstract

Using well-established methodology, D-glucose was transformed into a tribenzoyloxy cyclohexanone oxime derivative. Sodium azide treatment permitted the regiospecific exchange of the benzoyloxy group at a α-position relative to ketone oxime. Under standard Beckmann conditions the α-azido was oxime cleaved to provide an ω-dicyano compound.     

Total Synthesis of the Antiviral Peptide Antibiotic Feglymycin

An adaptable approach : The first highly convergent stereoselective synthesis of feglymycin (see structure) and its enantiomer is based on the coupling of repeating peptide fragments. The use of weakly basic conditions throughout the synthesis suppressed the epimerization of sensitive aryl glycine units. Feglymycin has strong anti‐HIV activity as well as potent (previously identified as weak) antibacterial activity against Staphylococcus aureus.

     

An Efficient Synthesis of Enantiomeric Ribonucleic Acids from D-Glucose

Enantiomeric oligoribonucleotides (= ent-RNA) up to a sequence length of thirty-five and consisting of the (L -configurated) nucleosides ent-adenosine, ent-guanosine, ent-cytidine, ent-uridine, and 1-(β-L -ribofuranosyl)thymine were prepared by automated synthesis from appropriate building blocks, carrying a known photo-labile 2′-O-protecting group. A simple large-scale synthesis of the new, prefunctionalized L -ribose derivative 5 from D -glucose (Scheme 1) and its straightforward conversion into the five phosphoramidites 28 – 32 and five solid supports 38 – 42 , respectively, were elaborated (Scheme 4). Within this project, a novel, superior strategy for the synthesis of the 2′-O-{[(2-nitrobenzyl)oxy]methyl}-substituted key intermediates 18 – 22 by regioselective alkylation of their 5′-O-dimethoxytritylated precursors 13 – 17 was developed. Furthermore, an improved set-up for the final light-induced cleavage of the 2′-O-protecting groups from the oligonucleotide sequences was designed (Scheme 5 and Fig. 1). The correct composition of all ent-oligoribonucleotides prepared was established by their MALDI-TOF mass spectra. The ¹H-NMR-spectroscopic data of a dodecameric ent-RNA sequence was in excellent agreement with the published data of its natural counterpart, synthesized by conventional methods. The known specific cleavage of a tetradecamer sequence by a 35mer ribozyme structure could be reproduced by ent-oligoribonucleotides, synthesized by the presented methods (Fig. 4).     

A Formal Total Synthesis of (-)-Brevisamide

A formal total synthesis of (−)-brevisamide has been achieved. The synthetic approach highlights a chemoselective asymmetric dihydroxylation and a one-pot Fraser-Reid epoxidation/PMB protection reaction sequence.     

A Total Synthesis of FK-506(1)

A total synthesis of FK-506 (1) is presented. The synthesis features a highly convergent approach utilizing a block coupling strategy. Top and bottom half sections of the molecule are coupled by addition of a vinyl cuprate with a spiroenone. The alpha-allyl aldol functionality is revealed by a reductive opening of the spiroenone system. The labile alpha,beta-diketoamide hemiketal portion of the molecule is prepared by a late stage generation and oxidation of a masked enediol. Top and bottom half segments are themselves derived by coupling of smaller subunits, resulting in a very convergent route.     

Asymmetric Total Synthesis of Fluvirucinine A(1)

Diastereoselective vinyl addition to an amide carbonyl group and amide enolate induced aza-Claisen rearrangement are the key steps in the first asymmetric total synthesis of fluvirucinine A(1) (1), the aglycon of fluvirucin A(1). Fluvirucins are a class of macrolactam antibiotics produced by actinomycete strains that show promising biological properties.