Dimethylphenylcarbamate

Starting from a collection of samples remarkably well resolved (alpha > 6) on Chiralcel OD (Cellulose tris(3,5-dimethylphenylcarbamate) coated on aminopropyl silica), a putative three-point enantiophore for binding to CSR was derived (Fig. 4-10). This enantiophore query was used to search (CFS 3D search) within a list comprising 4203 compounds tested on Chiralcel OD. From this search domain of CHIRBASE 3D, 191 structures were found to match the enantiophore. 

Chiralcel OD Cellulose tris(3,5-dimethylphenylcarbamate coated on amino-propyl silica. 

By the treatment of oat spelt xylan with phenyl or tolyl isocyanate in pyridine the fully fimctionahzed corresponding carbamates were prepared [416]. Xylan 3,5-dimethylphenylcarbamate showed higher recognition abihty for chiral drugs compared to that of the same cellulose derivative [417]. 

Chiralcel OD Cellulose tris(3,5-dimethylphenylcarbamate) coated on silica gel [11,19,67,68] Daicel, [67,68]... 

Chankvetadze, B., Yamamoto, C., Tanaka, N., Nakanishi, K., Okamoto, Y. (2004). High-performance liquid chromatographic enantioseparations on capillary columns containing monolithic silica modified with cellulose tris(3,5-dimethylphenylcarbamate). J. Sep. Sci. 27, 905-911. 

The chiral recognition ability of a CSP is quantitatively evaluated from the results of chromatographic separation of enantiomers. Figure 3.4 shows a chromatogram of the resolution of benzoin (19) on cellulose tris(3,5-dimethylphenylcarbamate). The (+)-isomer elutes first followed by the (—)-isomer complete baseline separation is achieved. The results of the separation can be expressed by three parameters—capacity factors (k1), separation factor (a), and resolution factor (Rs)—defined as follows ... 

Figure 3.4 Optical resolution of 19 on cellulose tris(3,5-dimethylphenylcarbamate) column 25 x 0.46 (i.d.) cm eluent hexane/2-propanol (90/10) flow rate 0.5 ml/min (i.d. = inside diameter).

The enantiomers of many compounds are eluted in reverse order on the 3,5-dimethylphenylcarbamates of cellulose (23x) and amylose (24n), suggesting that these two CSPs may be complementary in recognizing chirality. Many enantiomers unresolved on 23x can be resolved on 24n, and vice versa. Consequently, when two 23x and 24n columns were used for the resolution of 500 racemates, nearly 80% of the racemates were separated into enantiomers at least on either of 23x and 24n. 

Figure 3.28 Structures of 3,5-dimethylphenylcarbamates of cellooligosaccharides (29), maltooligosaccharides (30), and cyclodextrins (31).

Figure 3.29 CD spectra of (a) 3,5-dimethylphenylcarbamates of cellooligosaccharides (29) and 23x and (b) maltooligosaccharides (30) and 24n in THF. Concentration 1 mg/ml. (Reprinted with permission from Ref. 193. Copyright 1990 by the Chemical Society of Japan.)...

Tris(tribromoneopentyl) phosphate, 11 492 Tris(tribromophenyl) triazine, 11 467 Tris- 1-phenylethylcarbamate chiral stationary phase, 6 88t Tris-3,5-dichlorophenylcarbamate chiral stationary phase, 6 88t Tris-3,5-dimethylphenylcarbamate chiral stationary phase, 6 88t Trisaccahrides, 4 697 Trisanyl, 4 358t Trisaturates, 10 813 Trisazo dyes, 9 363... 

These polysaccharide-based stationary phases appear to be the most useful in organic, bio-organic and pharmaceutical analysis. Of the above-mentioned derivatives three of them, namely cellulose tris-(3,5-dimethylphenylcarbamate), amylose tris-(3,5-dimethylphenylcarbamate) and cellulose tris-(4-methylbenzoate), have very complementary properties and numerous publications have demonstrated that they have been able to achieve the chiral resolution of more than 80% of the drugs currently available on the market. " These CSPs are known under the commercial names, Chiralcel OD-H , Chiralpak AD and Chiralcel OJ , respectively (Figure 4). Their very broad enantiorecognition range is also the... 

Figure 3.1 Chemical structures of the current most successfully employed derivatised polysaccharide CSPs. (a) CHIRALPAK AD Amylose tris (3,5-dimethylphenylcarbamate) coated onto a silica support, (b) CHIRALPAK AS Amylose tris [(S)-a-methylbenzylcarbamate] coated onto a silica support, (c) CHIRALCEL OD Cellulose tris (3,5-dimethylphenylcarbamate) coated onto a silica support, (d) CHIRALCEL OJ Cellulose tris (4-methylbenzoate) coated onto a silica support.

Chankvetadze et al. prepared a 20-cm-long silica capillary column modified by in situ coating with amylase tris(3,5-dimethylphenylcarbamate) [199] for the fast separation of enantiomers. They showed the separation of 10 pairs of enantiomers. The monolith columns exhibit a slightly lower resolution but significant faster separation compared with a conventional 25 cm packed HPLC column. 

The progress toward enantiomerically pnre drngs makes the selective and rapid analysis of enantiomers an important issue, both for chiral parity determinations and for enantioselective bioanalysis. Chankvetadze et al. [198] performed enantioseparations within an analysis time of 1 min for each of two chiral compounds (1,2,2,2-tetraphenylethanol and 2,2 -dihydroxy-6,6 -dimethylbiphenyl) by nsing a homemade capillary column containing monolithic silica modified with amylose tris(3,5-dimethylphenylcarbamate) (Figure 17.10). 

FIGURE 17.10 Fast enantioseparation of (A) 1,2,2,2-tetraphenylethanol and (B) 2,2 -dihydroxy-6,6 -dimethylbiphenyl. Stationary phase monolithic silica modified with amylose tris(3,5-dimethylphenylcarbam-ate). Mobile phase n-hexane 2-PrOH (9 1 v/v). The UV detection was conducted at 254 nm. (Reprinted from Chankvetadze, B. et al., J. Chromatogr. A, 1110, 46, 2006. Copyright Elsevier, 2006. With permission.)... 

Musshoff et al. [35] developed a method for the enantiomeric separation of the synthetic opioid agonist tramadol and its desmethyl metabolite using a Chiralpak AD column containing amylose tris-(3,5-dimethylphenylcarbamate) as chiral selector and a n-hexane/ethanol, 97 3 v/v (5mM TEA) mobile phase nnder isocratic conditions (1 mL/min). After atmospheric pressure chemical ionization (APCI), detection was carried out in positive-ion MS-MS SRM mode. The method allowed the confirmation of diagnosis of overdose or intoxication as well as monitoring of patients compliance. 

Using amylose tris-3,5-dimethylphenylcarbamate as the chiral selector in enantioselective high-performance liquid chromatography, micropreparative resolution of the DHA racemate was achieved and the chromatographic behaviour in enantio-GC could be defined by coinjecting these references of definite chirality (Fig. 17.4) [13]. 

A single CSP cannot be used for the chiral resolution of all racemic compounds. Therefore, different CSPs were used for the chiral resolution of different racemates. To make this part easy and clear, Table 1 includes the names of 20 CSPs and their most frequent applications. However, some other interesting applications are possible. Upon screening about 510 racemic compounds described in the literature, we observed that 229 of them resolved completely and 86 partially on cellulose tris(3,5-dimethylphenylcarbamate), and the rest not at all. For amylose tris(3,5-dimethylphenylcarbamate) CSP, we screened 384 racemic compounds and observed that 107 resolved completely and 102 partially. Clearly, cellulose and amylose tris(3,5-diphenylcarbamate) CSPs have the ability to resolve about 80% of the racemic compounds investigated. 

Chiralcel OD-Hb Cellulose tris(3,5-dimethylphenylcarbamate) Alkaloids, tropines, amines, /i-adrenergic blockers... 

---