Nucleosides—XCV: Total synthesis of pentopyranamine D,the nucleoside moiety of blasticidin H

1-(4-Amino-3,4-dideoxy-β-d-ribo hexopyranosyluronic acid)cytosine was synthesized and its identity with the natural product pentopyranamine D was established.     

Total synthesis of nucleoside antibiotic. Ascamycin

Synthesis of ascamycin was achieved by the condensation of N⁶-t-butyloxy-carbonyl-2-chloro-9-(2′,3′-0-isopropylidene-5′-0-sulfamoyl-β-D-ribofuranosyl)adenine(4) with t-butyloxycarbonyl-L-alanylimidazole in the presence of Cs₂CO₃ in DMF as a key step.     

Total synthesis of spicamycin amino nucleoside

[formula: see text] The first total synthesis of spicamycin amino nucleoside 2 has been achieved. The aminoheptose unit 5 was prepared stereoselectively from myo-inositol, and the characteristic N-glycoside linkage was constructed by way of Pd-catalyzed coupling reaction of 5 with 6-chloropurine derivative 6.     

Total synthesis of rutamycin B, a macrolide antibiotic from Streptomyces aureofaciens.

Rutamycin B (2) was synthesized from three principal subunits, spiroketal 75, keto aldehyde 83, and aldehyde 108. First, triol 62 was assembled by Julia coupling of sulfone 56 with aldehyde 58 followed by an acid-catalyzed spiroketalization. The three hydroxyl functions of 62 were successfully differentiated, leading to phosphonate 75. The latter was condensed in a Wadsworth-Emmons reaction with 83, prepared in six steps from (R)-aldehyde 76, to give 92. Coupling of the titanium enolate of 92 with 108 afforded Felkin product 109 with high stereoselectivity in a process that is critically dependent on the presence of the p-methoxybenzyl ether in the aldehyde. Transformation of 109 via aldehyde 116 to vinylboronate 122 was followed by macrocyclization under Suzuki conditions to yield 123. Exhaustive desilylation of the latter yielded rutamycin B.     

Nucleosides and nucleotides. Solid-phase synthesis of oligonucleotides on an insoluble, macroporous carrier

Insoluble, macroreticular, highly cross-linked polystyrene with projecting mono-methoxytrityl chloride groups 4 was prepared and condensed with thymidine (TD ) as well as with 1-(2′-deoxy-ß-D-ribofuranosyl)-2(1H)-pyridone (II_d) to give the polymers 5 and 6 respectively, containing approximately 465 μmoles resp. 650 μmoles of bound nucleoside per gram of polymer. A standard procedure for removal of the products from the support is described. Condensation of the polymer-bound nucleosides 5 and 6 , respectively, with 3′-O-acetyl-thymidine-5′-phosphate ( 7 ) in the presence of mesitylenesulfonyl chloride (MS) and subsequent removal from the polymer yielded the dinucleoside phosphates T_d-T_d ( 9 ) and II_d-T_d ( 11 ) respectively. Condensation of the polymer 8 with 3′-O-acetyl-thymidine-5′-phosphate ( 7 ) in the presence of MS and cleavage of the polymer linkage gave the trithymidine diphosphate (T_d-T_d-T_d) ( 13 ). Phosphorylation of the polymer-bound nucleosides 5 and 6 with ß-cyanoethyl phosphate in presence of MS took place in 3′-position. Similarly the polymer-bound dinucleoside phosphates 8 and 10 gave 16 and 17 respectively.     

A total synthesis of oxetanocin,a novel nucleoside with an oxetane ring

Oxetanocin has been synthesized starting from cis-2-buten-1,4-diol through α- or β-D-oxetanosyl acetate as an important intermediate which has an α-(methyl oxalyloxy)methyl group at C₂-position.     

Total synthesis of lepidopteran A,self-defence substance produced by silkworm.

Lepidopteran, self-defence substance produced by silkworm (Bombyx mori), was synthesized by the solution method for confirmation of the proposed structure.     

Total synthesis of (+)-tubelactomicin A. 1. Stereoselective synthesis of the lower-half segment by an intramolecular Diels-Alder approach

[reaction: see text]. Starting from diethyl (R)-malate, synthesis of the lower-half segment of (+)-tubelactomicin A, a 16-membered macrolide antibiotic, has been achieved. The synthesis involved the highly endo- and pi-facial selective intramolecular Diels-Alder reaction achieved using a trisubstituted methacrolein derivative tethering a 10-carbon dienyne unit at the beta-carbon, which in turn was prepared from a known allylated malic acid derivative.     

Total synthesis of an antitubercular lactone antibiotic, (+)-tubelactomicin A

(+)-Tubelactomicin A (1), an antitubercular lactone, has been synthesized from (S)-citronellol (2) and 2-deoxy-l-ribonolactone (18) through intramolecular Diels-Alder reaction, Suzuki-Miyaura coupling, and Shiina macrolactonization.