Lim ligands

Figure 7.9. Lim ligands developed by Sasol position of R group not defined...

The so-called LIM ligands were claimed by Sasol for cobalt-catalyzed hydroformylation (Scheme 2.6) [21]. They represent P-alkyl derivatives of 4,8-dimethyl-2-phospha-bicyclo[3.3.1]nonane and can be produced as a mixture of diastereomers by radical-mediated /iti-Markovnikov addition of PHj to (S)- or (/ )-limonene and final reaction of the yielding LIM-H with a long-chain terminal olefin [22]. The last step can be initiated by a radical chain initiator (AINB) or proceeds with the assistance of a strong base [23]. 

A dose relative of the LIM ligands are phosphines of the VCH series (Scheme 2.7). Sasol patented this class of monophosphines accessed by radical-mediated addition of primary phosphines to 4-vinyl cyclohexene [25]. Some of these protocols have been conducted in a preparative 1/2 kg scale. 

Another group of bicyclic aliphatic phosphines has been introduced by Sasol [15], Their ligands are based on addition of PH3 to limonene (the R-enantiomer). A mixture of two diastereomeric compounds is obtained due to the two configurations of the methyl group at the C-4 position (Figure 7.9). The Lim-H compounds obtained can be functionalised at the phosphorus atom with the usual radical reactions with alkenes or substitution reactions of their conjugate bases formed after treatment with BuLi with electrophiles. 

Lim, H.-K., Hsieh, Y.L., Ganem, B., Henion, J. Recognition of cell-wall peptide ligands by vancomycin group antibiotics studies using ion spray mass spectrometry. J. Mass Spectrom. 1995, 30, 708-714. 

Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R. Evaluation of histamine HI-, H2-, and H3-receptor ligands at the human histamine H4 receptor identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther 2005 314 1310-21. 

Some 2 and 3 -fluoro analogues of Cl-IB-MECA have been investigated as A3 AR ligands (Lim et al. 2003). While the introduction of a fluorine atom at the 2 -position compromised both A3 AR binding and activation, the 3 -fluoro substitution generally resulted in partial agonism. Compound 27 is one of the few ligands... 

Jung EM, Lim JH, Lee TJ, Park JW, Choi KS, Kwon TK. 2005. Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). 

Based upon the above Michaelis—Menten type kinetic behavior, the visual observation of thiolate complex in a copper(I)-thiolate solution, and compatibility of soft thiolate and disulfide ligands with soft copper(I) (64—65), Lim et al. (66) postulated the following mechanism for the... 

Patel JV, Lim HS, Nadar S, Tayebjee M, Hughes EA, Lip GY. Abnormal soluble CD40 ligand and C-reactive protein concentrations in hypertension Relationship to indices of angiogenesis. JHypertens 2006 24 117-121. 

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