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Scalable De Novo Synthesis of Aldgarose and Total Synthesis of Aldgamycin N.

ABSTRACT: Since the accompanying study had shown that the introduction of the eponymous aldgarose sugar to the C5-OH group of the macrocyclic aglycone of aldgamycin N is most difficult, if not even impossible, the synthesis route was revised and the glycosidation performed at an earlier stage. To mitigate the "cost" of this strategic amendment, a practical and scalable de novo synthesis of this branched octose was developed. The glycoside formation required mild conditions; it commenced with the reaction of the aglycone with the trichloroacetimidate donor to give a transient orthoester, which slowly rearranged to the desired aldgaropyranoside. The presence of the polar peripheral groups in the product did not impede the selective late-stage functionalization of the macrolide ring itself: the contained propargylic alcohol entity was readily transformed into the characteristic acyloin motif of the target by a ruthenium-catalyzed trans-hydrostannation followed by a modified Chan-Lam-type coupling.

SUBMITTER: Spath G

PROVIDER: S-EPMC8048874 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Scalable De Novo Synthesis of Aldgarose and Total Synthesis of Aldgamycin N.

Späth Georg G Fürstner Alois A

Angewandte Chemie (International ed. in English) 20210303 14

Since the accompanying study had shown that the introduction of the eponymous aldgarose sugar to the C5-OH group of the macrocyclic aglycone of aldgamycin N is most difficult, if not even impossible, the synthesis route was revised and the glycosidation performed at an earlier stage. To mitigate the "cost" of this strategic amendment, a practical and scalable de novo synthesis of this branched octose was developed. The glycoside formation required mild conditions; it commenced with the reaction ...[more]

PMID: 33448589

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