Total synthesis of spicamycin.
The first total synthesis of one of the spicamycin congeners, SPM VIII (3), is described. A preliminary model study for construction of the characteristic N-glycoside linkage in spicamycin using tetra-O-benzyl-beta-D-mannopyranosylamine (13) and halopurines 5 revealed that Pd-catalyzed conditions successfully provided the coupling products 14 and 15 in good yields. It was also shown that thermal anomerization of the N-glycosides easily occurred, which resulted in the predominant formation of the beta-anomer as the thermodynamically favored compound, and the activation energy of anomerization of 15 was estimated to be ca. 30 kcal/mol. The novel aminoheptose unit of spicamycin 6 was prepared stereoselectively by carbon elongation of an acyclic aldehyde, prepared by ring cleavage reaction of a highly functionalized cyclohexane derived from naturally abundant myo-inositol. The Pd-catalyzed coupling reaction of the beta-heptopyranosylamine 6 with protected 6-chloropurine 5d, followed by deprotection, provided spicamycin amino nucleoside 2, whose condensation with dodecanoylglycine completed the total synthesis of 3. This study confirmed the proposed unique structure of a novel nucleoside antibiotic.
Suzuki
Tamotsu
T
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Suzuki
Sayaka T
ST
Yamada
Iwao
I
Koashi
Yoshiaki
Y
Yamada
Kazue
K
Chida
Noritaka
N
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D006027:Glycosides / Q000737:chemistry; D006031:Glycosylation; D007294:Inositol / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006027:Glycosides; D011684:Purine Nucleosides; C091123:SPM VIII; D007294:Inositol; D010165:Palladium; C015502:septacidin