Pyranoside oxygen atom

The total synthesis of apoptolidin was accomplished in the laboratory of K.C. Nicolaou. The key C12-C28 vinyl iodide fragment was prepared using the Schwartz hydrozirconation of an internal alkyne followed by trapping of the alkenylzirconium intermediate with iodine (I2). The vinyl iodide was formed as a 6 1 mixture of regioisomers. Under the reaction conditions, the methyl orthoester was converted to the methyl glycoside moiety at C21, which was presumably facilitated by the complexation of Zr with the pyranoside oxygen atom. 

Figure 16. Molecular structure of some antibiotic derivatives of 1-deoxynojirimy-cin. Here, the pyranosidic oxygen atom of glucose is substituted by nitrogen allowing...

This inclusion of the oxygen atom of the e-hydroxyl or e-hydroxyl group at C-o within the ring occurs for both aldohexo- and aldopento-pyranosides, and so no difficulty occurs in comparing the various members of these series. 

Such an attraction would overcome, at least in part, the conformational instability imposed by the erected oxygen atom. For pyranosides which are not deoxygenated at C-6, the added electron-withdrawing power of the hydroxymethyl (or acyloxymethyl) group at C-5 should increase the charge on C-5, thus favoring a-D-glycoside formation even more.M(b)... 

Bond lengths collected from experimental data in X-ray crystal-structure determination of methyl pyranosides (11) and other products (77) strongly support the above discussion. Oxygen atoms with an electron pair antiperi-planar to a C — 0 R bond definitely have shorter C—0 bonds whereas the C - 0 R bond is longer than normal. Interestingly, theoretical calculations have been carried out (11, 78) and the results are consistent with the above discussion and experimental observations. 

Reeves assigned a heavy unfavorable weighting to the close approach of three oxygen atoms ( A2 effect ) " encountered in methyl /3-D-manno-pyranoside. His weighting may be excessive, when it is considered that no... 

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