Phase total synthesis

SY Ko, RM Wenger. Solid-phase total synthesis of cyclosporine analogues. Helv Chim Acta 80, 695, 1997. 

Figure 12 A solid-phase total synthesis of the antimycobacterial cyclodepsipeptide kaha-lalide A. The synthesis relies on the Kenner safety-catch linker for attachment to the peptide backbone, followed by macrocyclative cleavage of the linear depsipeptide...

Scheme 1. Use of the polystyrene-based selenenyl bromide resin in the solid-phase total synthesis of peracetyl macrophylloside D (13). (Nicolaou, 2000) ...

The solid-phase total synthesis of (S)-zearalenone by Nicolaou et al. (372) started with the preparation of the resins 488 and 489 from the Merrifield resin (486, Scheme 9.1). Oxidation, followed by olefination of the resulting aldehyde, gave a polystyrene vinyl resin (487), which was converted into dibutyltin chloride 488. In this process, the stannylation reagent n-Bu2SnHCl was formed in situ from -Bu2SnCl2 and n-Bu2SnH2. Reduction of 488 yielded the polymer supported tin hydride 489. 

Scheme 23 Solid-phase total synthesis of verrucins A, B, and anacine [259]...

FIGURE 2.10 A solid-phase total synthesis of kahalalide A. The Kenner safety-catch sulfonamide linker was employed for backbone amide attachment. After assembly of the hnear peptide, safety-catch activation resulted in macrocyclative cleavage from the resin. 

Ciobanu, L.C. and Poirier, D., Solid-phase parallel synthesis of 17-substituted estradiol sulfamate and phenol libraries using the multidetachable sulfamate linker, J. Comb. Chem., 5, 429, 2003. Niggemann, J. et al.. Natural product-derived building bloeks for combinatorial synthesis. Part 1. Fragmentation of natural products from myxobacteria, J. Chem. Soc., Perkin Trans. 1, 2490, 2002. Bourel, L. et al.. Solid-phase total synthesis of kahalalide A and related analogues, J. Med. Chem., 48, 1530, 2005. 

More recently, Wang and co-workers reported on a solid-phase total synthesis of 1-p-methylcarbapenem 97 because of interest in its potent broad-spectrum antibiotic activity. In this total synthesis (Scheme 3.19), azetidinone 92, bearing a chiral auxiliary, was loaded onto polystyrene-diethyl-silane resin 91 to give 93, which was condensed with allyl bromoacetate to give supported azetidinone 94. Treatment with TMSCl in the presence of NaN(TMS)2 and diphenyl phosphorochloridate (DPPC) promoted a Dieckmann-type cyclization to give supported vinyl phosphate 95 with concomitant release of the chiral auxiliary. Vinyl phosphate resin 95 was treated with thiophenol to give supported 1-P-methylcarbapenem 96, which was released from the solid support upon treatment with tetra-H-butylammonium fluoride (TBAF). 

Lei M, Ma C, Wang YG. Solid-phase total synthesis of 1-fi-methylcarbapenem. Chinese Chem. Lett. 2003 14 6-8. 

Scheme 17.1 Bidirectional solid-phase total synthesis of AigTX-636. The monoprotected diamine was anchored to the resin by reduced amination, followed by adding the amino acid linker and aromatic head group under the standard coupling condition. The polyamine backbone was prolonged by repeated Fukuyama-Mitsunobu reactions. After adding the terminal arginine to the intermediate, the protected resin-bound molecule was released from the resin, and then the protecting group was removed to obtain the nature ArgTX-636...

Bourel-Bonnet, L., Rao, K.V., Hamann, M.T., and Ganesan, A. (2005) Solid-phase total synthesis of kahalalide A and related analogues. J. Med. Chem., 48,1330-1335. 

Ali, L., Ghulam, M., and Shaheen, F. (2008) SoUd-phase total synthesis of cyclic decapeptide phakellistatin 12. J. Nat. Prod., 71,1059-1062. 

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