Studies on the total synthesis of the macrolide antitumor agent rhizoxin. 2. Synthesis of the C14C26 segment

White, James D.; Holoboski, Mark A.; Green, Neal J.

doi:10.1016/s0040-4039(97)01781-4

Cited by 22 publications

(8 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Separation of 14 and 15 could be achieved by reversedphase HPLC, but it was found to be more convenient to process these as a mixture. Thus, methylation of 14/15 under standard conditions, followed by stannylcupration 14 using Bu 3 Sn(Bu)CuCNLi 2 15 and quenching with iodomethane gave 16 in 50% yield, together with ca. 20% of the minor diastereomer; the isomers were now readily separated by flash column chromatography.…”

Section: Methodsmentioning

confidence: 99%

Template-Directed Intramolecular C-Glycosidation. Synthesis of the Central Tetrahydrofuran Fragment of the Elfamycin Antibiotic Aurodox

Craig¹

1998

Synlett

View full text Add to dashboard Cite

A 14-step synthesis of the central tetrahydrofuran portion 4 of the elfamycin antibiotic aurodox is described, starting from the Dlyxose derivative 5. The key steps are template-directed intramolecular C-glycosidation by cation-mediated cyclisation of thioglycoside 6, and chelation-controlled addition of ethynylmagnesium bromide to aldehyde 8.As part of our programme to develop template-directed cyclisation reactions for C-glycoside synthesis, 1 we recently described 2 the silver(I) triflate-mediated conversion of thioglycosidic silyl enol ethers 1 into bicyclic C-glycosides 2 (Scheme 1). These transformations proceeded in good yields and with good diastereoselectivities; further synthetic elaboration gave the products (or their derivatives) of overall intermolecular delivery of nucleophilic carbon functionality to the anomeric centre, syn-with respect to the neighbouring hydroxyl group. Scheme 1We became interested in the application of this methodology to targetoriented synthesis, and chose fragment 4 corresponding to the central tetrahydrofuran portion of the elfamycin antibiotic aurodox 3 3 as an appropriate candidate. The retrosynthetic analysis is shown in Scheme 2; our plan was to introduce the dienyl side-chain by chelationcontrolled addition of an appropriate organometallic nucleophile to the aldehyde 8, which would be made from the product 7 of cyclisation of substrate 6, in turn derived from D-lyxose derivative 5.Compound 4 was a compelling goal for several reasons. Firstly, it possesses a syn-relationship between the anomeric C-C bond and the neighbouring oxygen atom on the five-membered ring, and as such seemed an ideal target molecule to exemplify our intramolecular delivery-based approach. 4 Secondly, it contains a fully oxygenated fivemembered sugar-derived template; we considered that the crowded environment created by the all-β disposition of the oxygenated substituents, and the potentially destabilising effect of these substituents on the anomeric cationic intermediate would provide a stern test for our strategy. Finally, unlike the major products 2 of the previous cyclisation reactions on six-membered templates, compound 4 bears a syn relationship between the ex-anomeric hydrogen atom and the substituent on the vicinal exocyclic stereocentre. Inspection of our pictorial model for the cyclisation process led us to believe that the antiselectivity observed previously would be reversed on account of the crowded nature of the substrate β-face, favouring 7 over 9 (Scheme 3), and we were keen to test this hypothesis. This Letter reports the results of these investigations. Scheme 3Target substrate 6 (Scheme 2) was readily assembled from protected Dlyxose 5 5 according to the route used in our methodological studies. 6

show abstract

Section: Methodsmentioning

confidence: 99%

Template-Directed Intramolecular C-Glycosidation. Synthesis of the Central Tetrahydrofuran Fragment of the Elfamycin Antibiotic Aurodox

Craig¹

1998

Synlett

View full text Add to dashboard Cite

show abstract

“…The first preparation of an acetylenosaccharide in low yields (17-22 %) by the use of dimethyl (diazomethyl)phosphonate and BuLi as base was described by Tronchet and co-workers as early as 1974 [70]. Later on, both fully protected aldehydo-sugars [71,72] and partially protected hemiacetals [73] were transformed (48-87 %) into terminal acetylenosaccharides by this method.…”

Section: By Eliminationmentioning

confidence: 99%

Acetylenosaccharides

Bernet¹,

Vasella²

2004

Acetylene Chemistry

View full text Add to dashboard Cite

“…Owing to the synthetic importance of alkynes, the sequence that allows the one-carbon chain homologation of aldehydes (R 2 = H) into terminal alkynes is especially useful and for that reason dimethyl diazomethylphosphonate (47) is frequently involved in the synthesis of natural products possessing complex molecular architecture. For example, 47 was employed in several multi-step syntheses of active compounds including modified forskolin, 184 immunosuppressive agents, [185][186][187][188][189] vitamin D3 metabolites, [190][191][192][193][194][195] alkaloids of various activity, [196][197][198][199] antibiotics, [200][201][202] natural toxins, 203 selective inhibitors of GABA transaminase, 204 cytotoxic agents [205][206][207][208][209][210][211][212] and others. [213][214][215][216][217] In complement with the rearrangement of diazoalkenes 54 that produces terminal alkynes, dimethyl diazomethylphosphonate (47) has also been used in intramolecular CH insertion [218][219][220][221][222][223] that leads to cyclopentenes formation (Scheme 23), 219 and intermolecular OH insertion with an alcohol...…”

Section: Alkynes 25; General Procedures (Table 4) 183mentioning

confidence: 99%