α-1-Tributyltin-O-2,3-bisacetyl-4,6-ethylidene-glucose as a convenient glycosidation reagent: An efficient synthesis of etoposide
The antineoplastic drug etoposide has been prepared by a chemically and operationally simple process. The salient reaction is the BF 3 etherate promoted, room temperature condensation of 4′-demethyl-4′-acetyl-epipodophyllotoxin 4, with α-1-Bu 3Sn-O-2,3-bisacetyl-4,6-ethylidene-glucose 6. The latter...
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| Published in: | Tetrahedron Vol. 52; no. 8; pp. 3049 - 3056 |
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| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Elsevier Ltd
19-02-1996
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| Online Access: | Get full text |
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| Summary: | The antineoplastic drug etoposide has been prepared by a chemically and operationally simple process. The salient reaction is the BF
3 etherate promoted, room temperature condensation of 4′-demethyl-4′-acetyl-epipodophyllotoxin
4, with α-1-Bu
3Sn-O-2,3-bisacetyl-4,6-ethylidene-glucose
6. The latter compound was prepared from 4,6-β-ethylidene glucose triacetate and Bu
3Sn-OMe obtained
in situ from (Bu
3Sn)
2O and dimethyl carbonate. A readily separable mixture of α and β-etoposide triacetate epimers was obtained where the desired β-epimer predominated. In contrast, 4,6-α-ethylidene glucose diacetate and
4, even at 0°C, gave an equimolar mixture of epimers. It is proposed that the stereochemical outcome may be attributed to electronic effects in the activated tin-glucose reagent.
BF
3·etherate promoted, room temperature condensation of 4′-demethyl-4′-acetylepipodophyllotoxin 4, with α-1-Bu
3Sn-O-2,3-bisacetyl-4,6-ethylidene-glucose, prepared from 4,6-β-ethylidene glucose triacetate and Bu
3SnOMe, gave a readily separable mixture of α and β-etoposide triacetate anomers where the desired β-anomer predominated. Subsequent deacetylation gave etoposide. |
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| ISSN: | 0040-4020 1464-5416 |
| DOI: | 10.1016/0040-4020(95)01122-6 |