Chromatography Diastereomeric forms

Initial efforts in this area involved the addition of BuaSnLi to fratw-crotonaldehyde and conversion of the racemic hydroxy stannane adduct to diastereomeric (-)-menthyloxy-methyl ethers by reaction with (-)-menthyloxymethyl chloride (Eq. 32) [52]. These dia-stereomers could be separated by careful chromatography. They formed diastereomeric anti, (Z) adducts with aldehydes upon heating to 130 °C. The results parallel those seen for the racemic OMOM allylic stannanes (Table 25). Formation of the (Z) double bond in these adducts is attributed to steric interactions between the allylic OR substituent and the adjacent stannane butyl groups in a chair-like transition state as pictured in Eq. (9). The excellent stereoselectivity of these additions is suggestive of a highly ordered transition state. 

Several barbiturates (e.g. 60-62) having two chiral centers exist in both enantiomeric and diastereomeric forms. The stereoisomers of 60 were obtained by Doran211 and exhibited different pharmacological activity.212 Four possible optical isomers of 61 were obtained by Miyano and Toki by enzymatic and chemical methods.193 Separations of diastereomeric mixtures were achieved by TLC and column chromatography on silica gel. The use of an adsorption of glucuronides of 61 on XAD-2 resin was advantageous for preliminary isolation of these compounds from urine.194... 

Chiral separations result from the formation of transient diastereomeric complexes between stationary phases, analytes, and mobile phases. Therefore, a column is the heart of chiral chromatography as in other forms of chromatography. Most chiral stationary phases designed for normal phase HPLC are also suitable for packed column SFC with the exception of protein-based chiral stationary phases. It was estimated that over 200 chiral stationary phases are commercially available [72]. Typical chiral stationary phases used in SFC include Pirkle-type, polysaccharide-based, inclusion-type, and cross-linked polymer-based phases. 

Z)-awh-4-Hydroxy-l-aIkenyl carbamates 363, when subjected to substrate-directed, vanadyl-catalysed epoxidation , lead to diastereomerically pure epoxides of type 364 (equation 99)247,252,269 qqjggg epoxides are highly reactive in the presence of Lewis or Brpnsted acids to form -hydroxylactol ethers 366 in some cases the intermediate lactol carbamates 365 could be isolated . However, most epoxides 364 survive purification by silica gel chromatography . The asymmetric homoaldol reaction, coupled with directed epoxidation, and solvolysis rapidly leads to high stereochemical complexity. Some examples are collected in equation 99. The furanosides 368 and 370, readily available from (/f)-0-benzyl lactaldehyde via the corresponding enol carbamates 367 and 369, respectively, have been employed in a short synthesis of the key intermediates of the Kinoshita rifamycin S synthesis . 1,5-Dienyl carbamates such as 371, obtained from 2-substituted enals, provide a facile access to branched carbohydrate analogues . 

For preparative-type resolutions (chromatography or other separation techniques) it is of vital importance that the derivatives can be cleaved smoothly to avoid chemical and optical losses. In addition, it would be advantageous to recover the CDA (see Section 3.2.1.2.). The Noe lactol (Tabic 1, entry 55) fulfills such criteria almost perfectly during the course of reaction with chiral alcohols to form diastereomeric acetals220. 

The mixture of the crude product hydrazone 138 and the excess of hydrazone 129 was used directly in an acidic acetalization reaction utilizing aqueous 3n HCl in a biphasic system and gave a diastereomeric mixture of sordidin (126) and 7-epi-sordidin (7-epi-126) in 84% yield over two steps in a 1.5 1 ratio. Gratifyingly, we succeeded in separating the desired sordidin epimers by preparative gas chromatography. As a result, both could be obtained in diasteromerically pure form (sordidin de > 99% 7-epi-sordidin de > 97%) and with a high enantiomeric excess for each epimer (ee > 98%). 

Biopolymers in Chiral Chromatography. Biopolymers have had a tremendous impact on the separation of nonsupernnposable. mirror-image isomers known as enantiomers. Enantiomers have identical physical and chemical properties in an achiral environment except that they rotate the plane of polarized light in opposite directions. Thus separation of enantiomers by chromatographic techniques presents special problems. Direct chiral resolution by liquid chromatography (lc) involves diastereomenc interactions between the chiral solute and the chiral stationary phase. Because biopolymers are chiral molecules and can form diastereomeric... 

Asymmetric cyclopropanation.3 The anion of ( + )-l reacts with 2-cyclohexene-1 -ones to form two diastereomeric adducts (2), which are separated by chromatography on silica gel. Cyclopropanation of optically pure 2a or 2b with the Simmons-Smith... 

The use of a cationic aza-Cope rearrangement in concert with a Mannich cyclization has also been applied to the total synthesis of enantiomerically pure (—)-crinine (359) (205). In the event, nucleophilic opening of cyclopentenoxide with the aluminum amide that was formed on reaction of (/ )-a-methylbenzyl-amine and trimethylaluminum gave the amino alcohol 485 together with its (15,25) diastereomer. Although there was essentially no asymmetric induction in this process, the diastereomeric amino alcohols were readily separated by chromatography, and the overall procedure therefore constitutes an efficient means for the preparation of enantiomerically pure 2-amino alcohols from epoxides. When the hydrochloride salt derived from 485 was treated with paraformaldehyde and potassium cyanide, the amino nitrile 486 was formed. Subsequent Swem oxida-... 

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