Trichloroethoxycarbonyl: a generally applicable protecting group

“…The ll,15-dicarbonates (2-8) was treated with dimethylamine in chloroform at room temperature for 10 minutes to obtain the 15-monocarbonates (9-15) in high yields. The 13C NMR spectra of these compounds (9)(10)(11)(12)(13)(14)(15) showed signals assignable to one carbonate group and the C-ll carbon signal (8 186.2-186.6) exhibited a down field shift compared to the corresponding Hitachimycin (1) Scheme 1. because ll-Ocarbonate bondage is more labile than ll-0-acyl bondage and we could not find out a suitable blocking group for 15-hydroxy group to be removed without suffering 1 1-Ocarbonate group.…”

Section: Synthesismentioning

confidence: 99%

“…It is notable that 1 1,15-di-Oethoxycarbonyl (3) and 15-O-methoxycarbonylhitachimycin (9) showed an increase ILS about twice, and 1 1 ,1 5-di-O-trichloroethoxycarbonyl (7), ll,15-di-O-vinyloxycarbonyl (8), 15-0-ethoxycarbonyl (10), 15-0-trichloroethoxycarbonyl (14) and 15-0-vinyloxycarbonylhitachimycin (15) also showed considerable improvement in ILS compared with that of hitachimycin. It is interesting that length of alkyl chain affects antitumor activities and the smaller ones exhibited higher activities.…”

Section: Tcetmentioning

confidence: 99%

Chemical modification of hitachimycin. II. Synthesis and antitumor activities of carbonate derivatives.

Shibata

Satsumabayashi²,

Sano³

et al. 1989

J. Antibiot.

View full text Add to dashboard Cite

Several carbonate derivatives of hitachimycin have been synthesized and evaluated their activities including antibacterial, cytocidal against HeLacells and in vivo antitumor against Sarcoma180. Some of these derivatives showed higher antitumor activity than hitachimycin. Amongthe derivatives, ll,15-di-O-methoxycarbonymitachimycin (2), ll,15-di-Oethoxycarbonylhitachimycin (3) and 15-0-methoxycarbonylhitachimycin (9) were most effective in in vivo assay.Hitachimycin (l)1) »nt is a macrocyclic lactam antibiotic isolated from the culture broth of actinomyces strain KM-4927, which shows antitumor3), antibacterial and antiprotozoal activities. Hitachimycin has an unique 19-membered ring lactam structure including trienamide and 1,3-diketone moieties0. The mode of action of hitachimycin and combined effect with bleomycin has been reported by Komiyama et al.*>5\ Since hitachimycin is hardly soluble in water and other organic solvents, it is difficult to utilize the drug for in vivo evaluation. In the course of the chemical modification of hitachimycin to obtain highly soluble and highly active derivatives, 1 1 and 15-0-acyl derivatives have been synthesized and some of them showed superior antitumor effect in vivo, as reported in a previous paper6). In this paper, we describe the synthesis of carbonate derivatives of hitachimycin and their in vivo antitumor activities against Sarcoma 1 80. SynthesisHitachimycin (1) has two hydroxy groups at the C-ll and C-15 positions in its molecule, the 1 1-hydroxy group being an enol of /3-diketone. Treatment of 1 with several alkyl chloroformate such as methyl70 , ethyl, propyl, «-butyl, iso-butyl, 2,2,2-trichloroethyl8) and vinyl chloroformate9) , in pyridine at room temperature gave the ll,15-dicarbonates (2~8), respectively. In the 13C NMRspectra of these carbonates (2~8), a paired signals assignable to carbonyl carbon of each carbonate group (3 154.9~156.2) and corresponded alkyl carbons were observed. Furthermore, up field shift (J 29.3m Hitachimycin was identified with stubomycin by their physico-chemical properties but the production strain of each compoundwas different2).

show abstract

“…Although treatment of 7 a with CAN resulted in ready removal of the PMB group, to give 7 b, oxidative removal of this group at latter stages of the synthesis was problematical. The more readily removable trichloroethoxycarbamoyl (Troc) group [6] was therefore used and was introduced by NH deprotonation of 7 b, followed by quenching with 2,2,2-trichloroethylchloroformate, to give 7 c. The imide 7 c was converted into the tetraester 8 a by ruthenium-catalyzed [22] cycloaddition with dimethyl acetylenedicarboxylate (DMAD) [7] and then into the diene 9 a by Diels ± Alder addition with cyclopentadiene. [8] The Troc group was cleanly removed in essentially quantitative yield upon treatment with zinc to give the bridge system 9 b.…”

mentioning

confidence: 99%

“…[4] Compared to intramolecular cyclizations, [5] however, the intermolecular hydroaminations of alkynes [6] is more difficult, and only a few approaches exist. [4] Besides the established stoichiometric aminomercuration/reduction method, [7] the only catalytic reactions known are those with mercury or thallium, [6a,b] and metallocenes of zirconium, [6c] lanthanide, [6d,f] and actinide.…”

mentioning

confidence: 99%

Novel U-Shaped Systems Containing an Imide-Functionalized Cleft for the Study of Solvent-Mediated Electron Transfer and Energy Transfer: Synthesis and Binding Studies

Head

Oliver

Look

et al. 1999

Angew. Chem. Int. Ed.

View full text Add to dashboard Cite

show abstract

Trichloroethoxycarbonyl: a generally applicable protecting group

Cited by 182 publications

References 6 publications

Synthesis of glycan fragments of glycoproteins using peracetylated N-allyloxycarbonyl-β-D-glucosamine and 1,6-anhydro-β-D-mannopyranose derivatives

Synthesis of glycan fragments of glycoproteins using peracetylated N-allyloxycarbonyl-β-D-glucosamine and 1,6-anhydro-β-D-mannopyranose derivatives

Chemical modification of hitachimycin. II. Synthesis and antitumor activities of carbonate derivatives.

Novel U-Shaped Systems Containing an Imide-Functionalized Cleft for the Study of Solvent-Mediated Electron Transfer and Energy Transfer: Synthesis and Binding Studies

Contact Info

Product

Resources

About