X-ray structure of 22.

¹³C NMR (100 MHz, D₂O, ref. internal CH₃CN, δ1.47 ppm) Δδ values (δ_C model — δ_C 1) of model compounds 2-7. “4b” and “5b” are ’virtual isomers’ of 4 and 5, respectively, by reversing the order of ¹³C δ assignments for the purpose of comparison with 1.

To further verify stereochemical assignments of the models, azide 15 was converted to the acetonide 23 (Scheme 3). The ¹H NMR spectrum of 23 showed the expected large diaxial vicinal couplings (δ 4.14, ddd, J 10.4, 8.0, 2.4 Hz; δ 3.83, ddd, J= 11.6,6.4, 2.4 Hz) for a syn-4,6-disubstituted 1,3-dioxane and large ¹³C chemical shift differences for the gem CH₃ signals of the isopropylidene group (δ 29.9, q; 19.7, q).10

The six models 2-7 were synthesized starting with serine (Scheme 1). O-TBS-N,N-dibenzylserinal (8), prepared from L-serine, was converted to epoxide 9 using the method of Concellón.6,7 Carbon chain extension of 9 by a BF₃•Et₂O-mediated epoxide opening with the anion derived from O-TBS propargyl ether afforded 10. Protecting group adjustment followed by Red-Al reduction of the triple bond gave E-olefin 11, which was treated with m-CPBA to give diastereomeric epoxides 12 and 13 in a ratio of 1:1.8.

The remaining four models were synthesized from the L-serine methyl ester derivative 16 (Scheme 2) using the complementary syn-selective epoxide formation7 to provide 17, the C2 epimer of 9. Chain extension of 17 was achieved as before to give propargyl alcohol 18 which was separately converted to E- and Z-allylic alcohols 19 and 20 by Red-Al reduction or hydrogenation over Lindlar catalyst, respectively. Epoxidation of olefin 19 using m-CPBA was less successful due to the lability of the diastereomeric products, however, oxidation of 19 with methyltrioxorhenium gave a mixture of distereomeric epoxides which was carried forward using Miyashita’s method followed by acetonide protection to give azides 21 and 22. Since neither of the two diaminotetraols anticipated from conversion of 21 and 22 were expected to show symmetry (C₁ space group), the configurational assignments of these molecules from NMR were in doubt. Fortunately, azide 22 crystallized as colorless needles (m.p. 138 °C) and X-ray analysis (Figure 2) provided the configuration of the 4-substitued (4R,5S)-2,2-dimethyl-5-azidodioxane ring [(13R,14S), zwittermicin A numbering]. It follows that 21 is the (4S,5R)-diastereomer.