A new approach to 2-deoxyglycosides permitting access to anthracycline glycosides specifically labeled at the 2′-position
✍ Scribed by Derek Horton; Waldemar Priebe; Marcos Sznaidman
- Publisher
- Elsevier Science
- Year
- 1989
- Tongue
- English
- Weight
- 340 KB
- Volume
- 187
- Category
- Article
- ISSN
- 0008-6215
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✦ Synopsis
Alkoxyhalogenation of L-rhamnal diacetate (1) with daunomycinone and Niodosuccinimide (NIS), and subsequent dehalogenation with tributylstannane, afforded 7-0-(3,4-di-O-acetyl-2,6-dideoxy-cu-L-arabino-hexopyranosyl)-daunomycinone (4) in 36% net yield. When the dehalogenation was conducted with DSnBu,, the 2'-axial deuterio analog (5) was obtained with -100% stereospecificity. A similar procedure with L-fucal diacetate (6) gave a 40% net yield of 7-0-(3,4-di-O-acetyl-2,6-dideoxy-cu-L-lyxo-hexopyranosyl)-daunomycinone ( 8). With DSnBu, as the reductant, the 2-axial deuterio analog (9) was obtained with -90% stereoselectivity.
The acetylated 3'-deamino-3'-hydroxy (8) and 3'-deamino-4'-epi-3'-hydroxy (4) analogs of daunorubicin were earlier synthesized in our laboratory2s3 by a Koenigs-Knorr coupling-reaction between daunomycinone and appropriate glycosyl chlorides. Based on daunomycinone, compound 8 was obtained in 78% yield by this method2. However, compound 4 was obtained as an inseparable mixture of CY and p anomers when mercuric salts were employed. The use of silver triflate gave the pure LY anomcr, but only in 14% yield. In order to improve the yields of compounds 4 and 8 and eliminate the use of mercury salts in the synthesis, an alternative approach is used here, The first step involves tram alkoxyhalogenation of the corresponding glycals with N-iodosuccinimide (NIS) and daunomycinone. This glycosidation method has proved useful with sugar derivatives, as demonstrated by Thiem et aL4, and with daunomycinone in earlier work from our group5. The second step employs dehalogenation with tributylstannane. This general sequence was used by Umezawa et al. 6 to obtain simple 2-deoxy-a-glycosides, and the steric course of dehalogenation of methyl 2-haloglycosides by DSnBu, has been studied in detail in our laboratory7.