Double coupling

For 2,4- or 4,5-disubstituted derivatives, there is a double coupling between the ttij and i>(C2X) or viC X) vibration on one hand and oscillations a)(, and n(C4X) on the other. These interactions induce, for the first one, two frequencies either higher (suite V) or lower (suite VIII), for the second, two other frequencies either higher (suite VI) or lower (suite VlII). 

A (1 — SO-coupled compound between methyl (3/ )-3-[(3 / )-3 -hydroxy-decanoyloxy]decanoate and 2-0-a-L-rhamnopyranosyl-o -L-rhamnopyra-nose, a rhamnolipid from Pseudomonas aeruginosa, expected to have various biological activities, was prepared by double couplings using 3,4-di-0-benzyl-2-0-chloroacetyl-a-L-rhamnopyranosyl fluoride (by the BFj- OEtj method). 

The utility of the stepwise, double-coupling procedure is demonstrated in the parallel synthesis of Tamoxifen derivatives on solid support [127] (Scheme 1-29). 1-Alkenylboronates thus obtained by a diboration-cross coupling sequence are further coupled with p-silyUodobenzene supported on polymer resin. Using this strategy, each position about the ethylene core is modified by the appropriate choice of alkyne, aryl halide, and cleavage conditions for the synthesis of a library of Tamoxifen derivatives. 

Another approach of this kind uses the approximate Brueckner orbitals from a so-called Brueckner doubles, coupled-cluster calculation [39, 40]. Methods of this kind are distinguished by their versatility and have been applied to valence ionization energies of closed-shell molecules, electron detachment energies of highly correlated anions, core ionization... 

Protein Sequencing. The xylanase protein sequence was obtained by stepwise automated E an degradation ter an initial double-coupling protocol, using an Applied Biosystems model 470A gas-phase sequenator equipped with an on-line Applied Biosystems model 120A PTH-amino acid analyzer 13). 

The incorporation of derivatives Fmoc-Ser[PO(OBzl)(OH)]-OH (18) and Fmoc-Thr[PO(OBzl)(OH)]-OH is best effected using uronium reagents such as HBTU/HOBt/ DIPEA and HATU/HOAt/DIPEA since both BOP and PyBroP failed to effect complete incorporation in comparative test couplings. 48 In a separate work, the BOP/HOBt/DIPEA coupling of Fmoc-Ser[PO(OBzl)(OH)]-OH was found to be only 85% complete after double coupling and the incorporation of the anionic phosphorodiester caused a decrease in the coupling efficiency of following residues. 94 Despite these potential problems, both Fmoc-Ser[PO(OBzl)(ONa)]-OH and Fmoc-Thr[PO(OBzl)(ONa)]-OH have been successfully employed for the Fmoc-based solid-phase synthesis of various Ser(P)- and Thr(P)-... 

Other a-fluorinated carboethoxy substrates have been utilized in Reformatsky reactions. Treatment of ethyl dibromofluoroacetate with aldehydes or ketones in presence of zinc and EtaAlCl gave diastereomeric a -brorno-a-fluoro /i-hydroxyalkanoic esters in good yield (49-77%) (equation 120)177. Use of 2 equivalents each of RCHO, Zn and Et2AlCl gave the double coupled products in good yield. 

Up to 8 equiv of Fmoc-protected amino add fluoride, at a concentration of 0.3 M in CH2C12, in the presence of DIPEA (1 equiv) were used. Single couplings of 30 min were performed. Only in the synthesis of trichotoxin A-50 were the introduction of Fmoc-Iva-F and the following Aib residue accomplished using double couplings of 1 h each. The yields of the final crude peptides were in the range 60-84%. 

A procedure for Boc-PNA manual synthesis is given below. If the coupling is incomplete (Kaiser test) double coupling is performed. The synthesis cycle is shown in Scheme 10 and the procedure is given in Table 1. 

The pentapeptide sequences were assembled on a Fmoc-Val-Pepsyn-KA-resin (0.08 mequiv-g 1) using a Biolynx synthesizer. Fmoc(Fmoc-Hmb)N-Gly-OH was incorporated using its pentafluorophenyl ester with HOBt catalysis for 45 min. Fmoc-Ala-OPfp was double coupled to the terminal (Hmb)tripeptide-resin for 2 h. All couplings not involving an Hmb-substituted residue were performed using standard 0.5 mmol scale coupling protocols. 

Double Coupling of Diazonium Compounds. Some compounds with an activated methyl group can form symmetric formazans with strong diazo compounds by double coupling ... 

When H-acid is used as a double coupling component, as in 13, in which reactive groups are present in both diazo functions, the resulting dye color ranges from blue to black. 

Definition of Ihe synthesis positions by spotting Fmoc-p-idanine-OPfp Double coupling... 

In some cases double coupling needs to be carried out to ensure completion of the reaction. Monitoring the coupling efficiency with the Kaiser test may be misleading due to the relatively acidic sulfonamide NH. 

Add this mixture to a vessel containing the resin-bound peptide (0.06 mmol, 0.25 g amino-peptide resin). After shaking for 2 h remove the solution by filtration and wash the resin with DCM and DMF (3 x 30 mL). Completeness of reaction is monitored using the TNBSA test. If necessary double coupling can be performed. 

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