Stereochemistry absolute

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

After the stmcture and absolute stereochemistry of cleavamine (111), C22H24N2, was estabUshed, its synthesis was shortly completed and impetus to unravel the stmcture of the dimeric bases (22) was bolstered (77). Again, the fragment, now only slightly modified from that originally present in secologanin (102), is readily seen in catharanthine (107). 

With its flexible and logical search language, REACCS can retrieve molecular stmctures, the atoms and bonds that are transformed ia a reaction, relative and absolute stereochemistry, the role (reactant, product, solvent, or catalyst) of a molecule ia a reaction, reaction data (eg, temperature and yield), hterature references, and keyword descriptions of reaction types. 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

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 substance chaetochromin A, structure A, has been shown by X-ray dif action to have the absolute configuration indicated in the structure. The CD spectra of A and the related compounds cephalochromin (B) and ustilaginoidin (C) are shown in the figure. Deduce the absolute stereochemistry of cephalochromin and ustilaginoidin trom these data, and draw perspective structures indicating the absolute configuration. 

Given the relatively rare appearance of oxetanes in natural products, the more powerful functionality of the Patemo-Biichi reaction is the ability to set the relative stereochemistry of multiple centers by cracking or otherwise derivitizing the oxetane ring. Schreiber noted that Patemo—Btlchi reactions of furans with aldehydes followed by acidic hydrolysis generated product 37, tantamount to a threo selective Aldol reaction. This process is referred to as photochemical Aldolization . Schreiber uses this selectivity to establish the absolute stereochemistry of the fused tetrahydrofuran core 44 of the natural product asteltoxin. ... 

The desilylacetylated qrcloadducts, produced from the reactions of trimethylsilyl-diazomethane with 3-crotonoyl-2-oxazolidinone or 3-crotonoyl-4,4-dimethyl-2-oxa-zolidinone, were transformed to methyl traws-l-acetyl-4-methyl-l-pyrazoline-5-car-boxylate through the reactions with dimethoxymagnesium at -20 °C. When the optical rotations and chiral HPLC data were compared between these two esters, it was found that these two products had opposite absolute stereochemistry (Scheme 7.39). The absolute configuration was identified on the basis of the X-ray-determined structure of the major diastereomer of cycloadduct derived from the reaction of trimethylsilyldiazomethane to (S)-3-crotonoyl-4-methyl-2-oxazolidi-none. 

From the data available it is cleat that diasteteoselective reactions of type ll) are very useful for control over absolute stereochemistry, hut they requite stoichiometric amounts of the chiral auxiliary. Reactions of type 13), on the other hand, have so far... 

Scheme 5 details the asymmetric synthesis of dimethylhydrazone 14. The synthesis of this fragment commences with an Evans asymmetric aldol condensation between the boron enolate derived from 21 and trans-2-pentenal (20). Syn aldol adduct 29 is obtained in diastereomerically pure form through a process which defines both the relative and absolute stereochemistry of the newly generated stereogenic centers at carbons 29 and 30 (92 % yield). After reductive removal of the chiral auxiliary, selective silylation of the primary alcohol furnishes 30 in 71 % overall yield. The method employed to achieve the reduction of the C-28 carbonyl is interesting and worthy of comment. The reaction between tri-n-butylbor-... 

Another critical stage in the synthesis has been reached. The previous sections have summarized the reactions leading to the synthesis of both domains of calicheamicin y[, each with the correct absolute stereochemistry and in a form suitable for further advance. We are now in a position to describe the union of key intermediates 8 and 9 (see Scheme 21). 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

When enantiomerically pure allyl p-tolyl sulfoxide is deprotonated and then treated with electrophilic 2-cyclopentenone, a conjugate addition occurs forming a new carbon-carbon bond with very high control of absolute stereochemistry (equation 25)65. See also Reference 48. Similarly, using more substituted enantiomerically pure allylic sulfoxides leads to virtually complete diastereocontrol, as exemplified by equations 26 and 27 the double bond geometry in the initial allylic sulfoxide governs the stereochemistry at the newly allylic carbon atom (compare equations 26 vs. 27)66. Haynes and associates67 rationalize this stereochemical result in terms of frontier molecular orbital considerations... 

Enantiomerically pure 3-tolyl-2-sulfinyl-2-cyclopentenone 37 undergoes smooth, mild and diastereoselective conjugate hydride addition with lithium tri(sec-butyl)borohydride to afford ultimately 3-tolylcyclopentanone 38 in 93% enantiomeric purity (equation 35)78. The absolute stereochemistry of product 38 is consistent with a chelated intermediate directing hydride addition from that diastereoface containing the sulfoxide lone pair. 

The absolute stereochemistry at the sulfoxide sulfur atom in some /J-phenylsulfinyl radicals (prepared in situ by treating 2-bromo-3-phenylsulfinylbutanes with tributylstan-nane) controls the stereochemistry (i.e., cis vs. trans) of the olefinic products which are formed104. Implicit in this result is that loss of the sulfinyl group occurs more rapidly than rotation about C-2-C-3 of the intermediate radical105. 

Roseophilin (273), a deeply red-colored pentacyclic compound isolated from the culture broth of Streptomyces griseoviridis, is a novel antitumor antibiotic. Compound 273 possesses a topologically unique pentacyclic skeleton, consisting of a 13-membered macrocycle incorporated in an ansa-bridged azafulvene, which in turn is linked to a conjugated heterocyclic ring system. The absolute stereochemistry of roseophilin, as depicted in Fig. 9, was unknown until the first total synthesis published by Tius and Harrington in 2001 [125]. All syn-... 

Posner G. H., Bull D. S. Recent Advances in Control of Absolute Stereochemistry in Diels-Alder Cycloadditions of 2-Pyrones Recent Res. Dev. Org. Chem. 1997 1 259-271... 

The polyene macrolide filipin was isolated in 1955 from the cell culture filtrates of Sterptomyces filipinensis, and was later shown to be a mixture of four components [36]. Although too toxic for therapeutic use, the filipin complex has found widespread use as a histochemical stain for cholesterol and has even been used to quantitate cholesterol in cell membranes [37]. The flat structure of filipin III, the major component of the filipin complex, was assigned from a series of degradation studies [38]. Rychnovsky completed the structure determination by elucidating the relative and absolute stereochemistry [39]. The total synthesis plan for filipin III relied heavily on the cyanohydrin acetonide methodology discussed above. 

Furusaki, A., Hashiba, N. and Kurosawa, E. 1979. The structures and absolute stereochemistry of two halogenated chamigrenes from the red alga Laurencia majuscula Harvey. Tetrahedron Lett. 879-882. 

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