MBHA resin

Three generations of dendritic phosphines have been prepared from 3,5-diaminobenzoylglycine and 9-fluorenylmethoxycarbonyl-L-phenylalanine. The dendrimers were then attached to MBHA resin, treated with CH20 and Ph2PH, and converted to their Rh complexes. The polymer-supported complexes are excellent catalysts for the hydroformylation of alkenes, which could be recycled.283 The bidentate diphosphine A,A-bis-(P-(phosphabicyclo[3.3.1] nonan) methyl)aniline was prepared by phosphanomethylation of aniline. It forms a Rh-complex which is a highly regioselective catalyst in the hydroformylation of citronellene.284... 

Rink amide MBHA resin was purchased from Novabiochem, substitution = 0.54 mmol/g, lot A20678. 

Boc-Cys-Tyr[Z(Br)]-Ile-Gln-Asn-Cys-Pro-Leu-Gly-MBHA-resin [prepared from the corresponding S-Fm-protected resin-linked peptide (50-60mg, 0.35mmol/g, 19 nmol) by treatment with piperidine/ DMF/[5-ME (10 10 0.7) at 25 °C for 3 h] was suspended in pH 8 buffered DMF (3 mL) in an open vessel at 25 °C for 1 h, washed, deblocked with TFA/CH2C12, and cleaved with HF/anisole (9 1) at 0 °C for 1 h to provide the crude peptide yield 16 xmol (88%). This material was purified by MPLC on a Lobar RP-8 column yield 8.5 xmol (53%) the product was characterized by amino acid analysis and HPLC. 

The peptide resin Boc-Cys(Acm)-Arg(Tos)-Gly-Asp(OCy)-Phe-Cys(Acm)-MBHA-resin (0.5 mmol) was swollen with CH2a2 (10 mL) and suspended in DMF (10 mL). A soln of I2 (381 mg, 1.5 mmol) in MeOH (10 mL) was added and the mixture was stirred for 3h at rt. The resin was washed repeatedly with DMF and CH2Cl2/MeOH (1 1) and dried. It was then treated with HF/anisole (95 5) at 0°C for 1 h. After removal of the HF, the residue was washed repeatedly with Et20 and extracted with 5% AcOH, followed by lyophilization. The product was purified by HPLC and converted into its hydrochloride by repeated lyophilization from HCI-containing H20 yield 51 mg (16%) [a]D28 —68.8 (c 1.0, H20) the product was characterized by amino acid and MS analysis. 

Table 1 Optimized Protocol of the Synthesis of Selenocysteine Peptides on Rink-Amide-MBHA Resin According to the Fmoc Strategy 10 ...

Scheme 46 Cleavage of Peptides Containing Nucleo Alanines Prepared on MBHA Resin 83 ...

On-Resin Alkylation of Aa-Trt-Xaal-MBHA-resin l45l... 

The MBHA resin (substitution 0.63 mmol-g 1) was acylated in CH2C12 with the Boc N-protected linker 15 (2 equiv) in the presence of BOP as coupling agent and DIPEA as base. After 4 h and classical washings, the coupling was controlled by Kaiser s test. The protected resin 16 was ready for classical solid-phase synthesis. 

Peptide Ac-AKEAAHAEAAEAA-NH2 was synthesized using Boc chemistry on MBHA resin (100-200 mesh, 1% DVB, substitution level 0.53 mmol-g 1). Purification was carried out by HPLC on a 2.2-cm Vydac C18 column using a gradient of MeCN/H,0 in 0.1% TFA (5 to 40% over 40 min) at a flow rate of SmL-min Mesoporphyrin IX was converted into the iron(III) complex by refluxing with excess Fe(OAc)2 in AcOH.11"1 The bis(4-nitrophenyl) ester of iron(III) mesoporphyrin IX was subsequently prepared using the method of Collman et al.12001... 

Support-bound 1,2-diamines can be readily converted into imidazolidinones by treatment with carbonyl diimidazole [128,129]. The required diamines have been prepared on cross-linked polystyrene by reduction of peptides bound to MBHA resin with borane. Similarly, bicyclic imidazolines have been prepared from triamines and thiocarbonyl diimidazole (Entry 10, Table 14.3). Dehydration of polystyrene-bound monoacyl ethylene-1,2-diamines yields 4,5-dihydroimidazoles (cyclic amidines, Entry 5, Table 13.18). Several groups have reported the synthesis of 2-aminoimidazol-4-ones from resin-bound amino acid derivatives (e.g., Entry 6, Table 15.11). Most of these compounds are, however, unstable, and slowly decompose if dissolved in DMSO (Jesper Lau, private communication). 

MBHA resin 3. HF, p-cresol, butane-1,4-dithiol 4. Boc-OSu, DMSO, TEA SCH2CH2CONH2 ... 

MBHA resin hydrochloride (NH2 0.47 mequiv-g 3.4g) was washed with 5% DIPEA/CH2C12... 

Amide derivatives of benzothiazepinone 108 were prepared by solid-phase synthesis. Cleavage of 108 from the A-methylbenzhydryl (MBHA) resin was done with HF/anisole (Figure 13) <1999TL4939>. 

Coupling of Boc Amino Acids to MBHA Resin to Introduce the First Position of Diversity... 

Cleavage of Resin-Bound Heterocyclic Libraries from the MBHA Resin... 

Methylbenzyhydramine (MBHA) resin (1.18 g, 0.85 meq amino groups/g resin) was weighed into the reaction vessel and washed with two portions of chloroform (26 ml each). The resin was prewashed with 22% thioanisole (5 ml)/66% trifluoroacetic acid (TFA) in 14 ml dichloromethane (DCM) for 5 minutes, and then deprotected for 30 minutes with the same thioanisole/TFA mixture. The resin was washed with three portions of chloroform (20 ml each), two portions of 2-propanol (26 ml each) and two portions of DCM (26 ml each). The resin was neutralized with two portions of 12% diisopropylethylamine (DIPEA) (26 ml each), and then washed with four portions of DCM (26 ml each), followed by two portions of 1 1 DCM dimethylformamide (DMF) (26 ml each). A solution of a Boc-protected amino acid (2.5 mole equivalents) and 1-hydroxybenzotriazole (HOBt) (2.5 mole equivalents) was introduced as a solution in 10 ml DMF, and DCC was added (256 mg in 6 DMF). Coupling was allowed to proceed for three hours,... 

As solid support use Rink-amide MBHA resin (0.6 mmol/g, 100-200 mesh, MultiSynTec, Bochum, Germany) to obtain C-terminal peptide amides and Wang-resin (1.2 mmol/g, 100-200 mesh, MultiSynTec) or 2-chlorotrityl chloride resin (1.5 mmol/g, 100-200 mesh, Novabiochem, Merck KGaA, Darmstadt, Germany) to produce C-terminal free acids. 

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