Epoxides orientation

A mechanism for the stereoselectivity of the diastereoisomers of BPDE by duplex DNA is postulated. It entails a series of processes The diol epoxide intercalates with the epoxide oriented... 

Cephalostatins 14 and 158 (Figure 5) are related to cephalostatins 2 and 3 respectively by a-epoxidation at C-14 -15 dehydration of the C-9 alcohol, and hydroxylation at C-8 . Cephalostatins 14 and 15 display reduced activity, with mean panel GI50 of 100 and 68 nmolar respectively, perhaps due to the epoxide orientation - with steroidal bufadienolides, the p-epoxides are more cytotoxic. 

To predict the product of a Sharpiess asymmetric epoxidation, orient the molecule so that the allylic hydroxyl group appears in the upper right corner (Figure 14.3). When positioned in this way, (+)-DET gives epoxide formation above the plane, and (-)-DET gives epoxide formation below the plane. 

The stereochemistry of epoxidation of 5j5-steroids is changed from to predominantly a by the presence of an a-oriented hydroxyl group. The magnitude of this hydroxyl effect is less in polar solvents, as shown by the... 

The cleavage of steroidal epoxides with Grignard reagents leads exclusively to alcohols with the tra 5-diaxial orientation of the hydroxyl group and the newly introduced alkyl group. °... 

FIGURE 2.6 The procarcinogen benzo[a]pyrene oriented in the CYPlAl active site (stereo view) via n- n stacking between aromatic rings on the substrate and those of the complementary amino acid side chains, such that 7,8-epoxidation can occur. The substrate is shown with pale lines in the upper structures. The position of metabolism is indicated by an arrow in the lower structure (after Lewis 1996). 

Fig. 12.7. Alternate orientations of 3-methylbut-3-en-l-ol (3a) in the transition state for Ti-mediated epoxidation. Angle 9 is the inter-ring angle of the spiro rings. Reproduced from J. Org. Chem., 67, 1427 (2002), by permission of the American Chemical Society.

The stereochemical outcome of the reaction of 1-43, formed from 1-40 by desily-lation, can be explained by assuming a pseudoequatorial orientation of the epoxide moiety in a pseudo-chair-chairlike transition state 1-44 which, after being attacked by the phenolic oxygen, furnishes the correct trans-fused stereoisomer 1-41 (Scheme 1.12). The conformation 1-45, which would lead to 1-46 seems to be disfavored. 

The sense of the enantioface selection of olefin in Mn(salen)-catalyzed epoxidation is determined by two factors the olefin s approaching path, and its orientation. 

As discussed above, olefins were initially proposed as approaching the oxo-Mn center along path a, with an orientation directing their bulkier substituent away from the C3(C3 )-substituent (see Scheme 14). It is noteworthy that path a runs over the downwardly bent benzene ring. Later, Jacobsen et al. proposed path b for the epoxidation with (26) possessing /-butyl groups at C5 and... 

Figure 19. Perpendicularity of the PAH and the base. Conformations of trans-diols. The steric hindrance in a bay region will cause hydroxyl or other substituents (such as DNA) to lie in an axial orientation. Sites where this occurs are marked "a". Those sites where there is no steric hindrance are marked "ae" (axial or equatorial). The conclusion is that when a diol epoxide alkylates DNA the base on DNA will be bonded axially to the PAH group.

Figure 6. Optimum binding orientations of BPDE l(+) intercalated with the epoxide in the major (a) and minor (b and c) grooves in +OG,G C4. (c) Relative values of the electrostatic potential are...

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