Stereochemical assignments

Absolute Stereochemistry Absolute stereochemical assignment of each stereocenter (R vs S) Cahn-Ingold-Prelog Convention (sequence rules)... 

Additional compounds having similar biological activities and stmctural components were isolated resulting in the recognition of PGs as a family of closely related compounds. Stmctural and stereochemical assignments of PGE and PGF, were confirmed by x-ray crystallographic analysis of their... 

In the case of thienamycin (Fig. lb) the absolute stereochemistry at C-5 was unambiguously deterrnined from the ene-lactam (16). The resultant (R)-aspartic acid (17) demonstrated that the absolute stereochemistry at C-5 of thienamycin is (R), corresponding to that found in the C-5 position of both penicillins and cephalosporins. Confirmation of the stereochemical assignments in both thienamycin (2) and the olivanic acid MM 13902 (3, n = 0) has been confirmed by x-ray crystallography (19,21,22). The stmctural determination of the nonsulfated derivatives from S. olivaceus (23), PS-5 (5) (5), the carpetimycins (6), and the asparenomycins (7) followed a similar pattern. 

The stereochemical assignment is based on the comparison of the product with the pure cis and trans isomers (128 and 129) of the enamine prepared by the base-catalyzed elimination of the mesitoate esters of the d/-erythro-2-(4-morpholino)-l,2-diphenylethanol (130) and the <7/-threo-2-(4-morpho-lino)-l,2-diphenylethanol (131). 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

The only result in Table 2 that is difficult to rationalize is the (Z)-2-butenylboration of (S)-2,3,3-trimethylbutanal, that apparently proceeds preferentially (60%) by way of transition state 3 or 4. It would be expected, however, and Hoffmann s calculations indeed predicted21, that the (35,45)-isomer should be the major product of this reaction (via transition structure 5). Stereochemical assignments in this case were based on 13C-NMR analysis3211, and must be regarded as tentative. Further experimentation may be required to clarify this point. 

After 12 hours at 4 kbar. this reaction provided only 35% of a 63 27 mixture of 22 and a compound which was tentatively assigned structure 23. It is assumed that 23 derives from epimerization of 21 prior to reaction with (aS,S,S)-5l0b. Whether this stereochemical assignment is correct or not, this result shows that 5 may have problems with configurationally labile aldehydes in demanding cases of mismatched double diastereosclcction. For further examples of double asymmetric induction with 5 or related reagents, see refs 31, 34 and 47. 

The nOe experiment is one of the most powerful and widely exploited methods for structure determination. nOe difference (NOED) or the two-dimensional experiment, NOESY, is used extensively for stereochemical assignments. It provides an indirect way to extract information about internuclear distances. The other use of nOe is in signal intensification in certain NMR experiments, such as the broad-band decoupled C-NMR experiment. 

The nOe difference and ID H-NMR spectra (in C5D5N) of podophyllo-toxin are shown. Justify the stereochemical assignments of the C-2, C-3, and C-4 asymmetric centers based on the nOe data, assuming that the C-4 proton is -oriented.. ... 

The nOe difference measurements not only help in stereochemical assignments but also provide connectivity information. A large nOe at 8 6.91 (G-8H), resulting from the irradiation of the methyl singlet of the methoxy group (8 3.94), confirms their proximity in space. This nOe result is consistent with structure A for the coumarin. 

CLOUGH j M and pattenden g (1983) Stereochemical assignment of prolycopene and other poly-c isomeric carotenoids in fruits of the tangerine tomato Lycopersicon esculentum var, Tangella J Chem Soc Perkin Trans, 1, 30121-18. 

Clough, J.M. and Pattenden, G., Stereochemical assignment of prolycopene and other poly-z-isomeric carotenoids in the fruits of the tangarine tomato Lycopersicum esculentum var. Tangella, J. Chem. Soc. Perkin Trans. I, 3011, 1983. 

Chemical shifts and coupling constants have been used for structural, conformational and stereochemical assignments and preferences and for the establishment of the four-membered ring sulfone effect . ... 

Thorough analysis of the coupling constants suggests that vicinal and cross-ring coupling can be valuable when used for stereochemical assignments in thietane oxides and dioxides, provided one takes into consideration the conformational changes and the substituent effects . 

Following a detailed NMR study of the 3-substituted thietane dioxides 188 it was concluded that the three-bond coupling constants can be safely used for stereochemical assignments in this series in particular the 7rih4<4Hz (Table 7, R =H, X = C) is consistent with an equatorial-equatorial interaction. This indicates an axial preference for the 3-substituent R (i.e. 188b) in both liquid and solid phases, and also suggests that the ring is puckered . 

Reaction of estrone (2) with an excess of the lithium reagent from 3-iodofuran gives intermediate diol 3. The stereochemical assignment follows from the well-known propensity of steroids for attack from the less-hindered backside (a) of the molecule. Acylation of 3 with acetic anhydride then affords the estrogen estrvfurate (4).1... 

Figure 3. Conformation and stereochemical assignment of anti-and syn- BPDE. Reagents (i) t-BuSNa (ii) Ac20.

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