D-O-E-rings

Double intramolecular S Ai reaction leads to a model bicyclic C-O-D-O-E ring, as shown in Eq 9 9 " Synthesis of a model 22-membered AEl-C-0-D ring of vancomycin using similar strategy has been reported Totiil synthesis of vancomycin has been accomplished by Nicolaon and coworkers ... 

Scheme 2-3. Stereochemical features of the vancomycin structure. The AB-ring (chiral axis) and the C-O-D-O-E-rings (chiral planes) fixate the heptapeptide aglycon in a rigid comformation.

SNAr-medialed D-O-E-ring formation and deprolecdon steps... 

Both total syntheses of Evans et al. and Nicolaou et al. first perform synthesis of the AB/C-O-D-ring systems before condensation with the D-O-E ring system. The Evans et al. route was extended by several synthetic steps by the conversion of the 2-OH-group of Hpg and the conversion of nitro substituents after SnAt into hydrogen substituents. Problems developed with the transformation of the C-terminal amide into the carboxy function during deprotection steps. In contrast, Nicolaou et al. had to face the relatively moderate atroposelectivities and had to solve the somewhat obscure conversion of the triazene into a phenolic group. Both syntheses have been compared and discussed in the literature. ... 

Currently, it is the Evan s group, however, who can claim to have produced the most advanced compound in a vancomycin synthesis. They us an oxidative coupling to produce the C-O-D ring in compound 12, [18] and a SNAr cyclization to produce the complete AB-C-O-D-O-E system 13. [19] The latter transformation favors the atropisomer corresponding to the vancomycin D-O-E atropisomer by a 7 1 factor, in a reaction that was surprisingly efficient (90 % yield of combined cyclization products). 

For example, macrocyclizations of the D-O-E macrocycle (14-membered ring) which should, in principle, be easier, afforded low to modest yields of products a) M.J. Crimmin, A. G. Brown, Tetrahedron Lett. 19SK), 31, 2017 and ensuing paper b) A. J. Pearson, H. Shin, J. Org. Chem. 1994, 59, 2314. In model systems (Ref. 10a and 11c), the Nicolaou group achieved far inferior yields during the same type of macro-cyclization. Attempts to form the AB system by itself through macrocyclization failed A. G. Brown, M. J. Crimmin, P. D. Mwards, J. Chem. Soc., Perkin Trans. 1, 1992, 123. 

Horita, K., Nagasawa, M., Sakurai, Y, and Yonemitsu, O. (1998) Synthetic studies on halichondrin B, an antitumor polyether macrolide isolated from a marine sponge. 9. Synthesis of the C16-C36 unit via stereoselective construction of the D and E rings. Chem. Pharm. Bull., 46,1199-1216. 

This type of ring interconversion is represented by the general expression shown in Scheme 15. Analogous rearrangements occur in benzo-fused systems. The known conversions are limited to D = O in the azole system, i.e. cleavage of the weak N—O bond occurs readily. Under the reaction conditions, Z needs to be a good nucleophile in its own right or by experimental enhancement (base catalysis, solvent, etc.) and Z is usually O, S, N or C. 

The relationship between 20 and reserpine (1) is close like reserpine, intermediate 20 possesses the linear chain of all five rings and all six stereocenters. With the exception of the 3,4,5-tri-methoxybenzoate grouping, 20 differs from reserpine (1) in one very important respect the orientation of the ring C methine hydrogen at C-3 in 20 with respect to the molecular plane is opposite to that found in reserpine. Intermediate 20 is a reserpate stereoisomer, epimeric at position 3, and its identity was secured by comparison of its infrared spectrum with that of a sample of (-)-methyl-O-acetyl-isoreserpate, a derivative of reserpine itself.9 Intermediate 20 is produced by the addition of hydride to the more accessible convex face of 19, and it rests comfortably in a conformation that allows all of the large groups attached to the D/E ring skeleton to be equatorially disposed. 

Interestingly, we were intrigued by the ESI mass spectrum of the compound, as the observed base peak consisted of [M-S02+Na]+. This led us to explore a thermal retro-Diels-Alder reaction that could afford the desired enone 69. It is noteworthy that the chemistry of cyclic enol-sulfites would appear to be an under-explored area with a few references reporting their isolation being found [57]. At last, we were also able to prepare epoxy ketone 70 from 69 in three steps, albeit epoxidation did not take place unless the TES group was removed. Spartan models reaffirmed our initial conformational assessment of enone 69 and epoxy ketone 70, which contain sp3-hybridized C8a and s/r-hybridized C8b (p s e u d o-. v/r - h y b r i d i zed C8b for 70) at the AB-ring junction (Fig. 8.12) and displayed the desired twisted-boat conformation in A-ring. 

Figure 12, Sketch of the high pressure sound velocimeter (A) constant temperature bath (B )bomb stand (C) pressure bomb (D) plug (E) transmitting transducer (F) reflector (G) O-ring (112)...

Figure 3.3 Side- and top-view of the in situ infrared autoclave. A IR window B Turbine rotor C Reagent addition D Thermocouple E Opening between upper and lower chamber F Electrical heaters C Kalrez O-rings (from Ref [6], reproduced by permission of Elsevier).

Figure 7.2 Silicate anion structures (o) orthosilicate, (6) pyrosilicate, (c) three-silicate ring, (d) six-silicate ring, (e) pyroxene, (/) amphibole, and (g) phyllosilicate.

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