Chisholm et al. 10.1073/pnas.0602662103.

Supporting Information

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Supporting Experimental Procedures

General. 1H and 13C {H} NMR experiments were carried out with a Bruker DPX-400 or 500 spectrometer equipped with a 5-mm broad-band probe. Preparative gel-permeation chromatography (GPC) measurements were carried out on a Waters 1525 binary HPLC pump and Waters 410 differential refractometer equipped with an ultrastyragel 100-Å 19 × 300-mm preparative column. The GPC was eluted with CHCl3 at 35°C running at 3 ml/min. MALDI-TOF was performed on a Bruker Reflex III mass spectrometer operated in linear, positive ion mode with a N2 laser. 2,5-Dihydroxybenzoic acid (DHBA) was used as matrix. Electrospray ionization (ESI) MS was performed on a Bruker Esquire ion trap mass spectrometer equipped with an orthogonal electrospray source operated in positive ion mode. Samples were prepared in a methanol solution and infused into the electrospray source at a rate of 10 mml•min–1. Optimal ESI conditions were as follows: capillary voltage was 3,500 V, source temperature was 250°C, and ESI drying gas was nitrogen. The ion trap was set to pass ions from m/z 50-2,200 amu. Data were acquired in continuum mode until acceptable averaged data were obtained.

Preparation of Polystyrene-Supported (PS) Catalyst: PS Amino Magnesium and Zinc Catalyst.

(i) Zinc catalyst: PS amine (as defined above, 0.50 g, 0.79 mmol) was suspended in benzene (10 ml) under a nitrogen atmosphere. Et2Zn (1 M, 3 ml, 3 mmol) was added, and the suspension was stirred at 60°C for 10 h. The beads were then filtered off, washed with benzene (two times, 10 ml) and hexane (10 ml), and dried under vacuum at 60°C. The product (0.57 g) was a yellow-colored powder with reduced absorptions at 3,060 cm–1 (N-H) compared with the PS-C6H4CH2NH2 starting material. The elemental analysis gave Zn 1.77 mmol/g.

(ii) Magnesium catalyst: To a tetrahydrofuran (THF) solution (10 ml) of MeMgCl (3.0 M, 3.0 ml, 9.0 mmol) was added 8 ml of 1,4-dioxane to form white precipitate. After being stirred for 4 h, the solution part was filtered out and added into a THF suspension (10 ml) containing PS amine (as defined above; 0.50 g, 0.79 mmol). The reaction mixture was stirred at 60°C for 10 h. The beads were then filtered off, washed with THF (two times, 10 ml) and benzene (10 ml), and dried under vacuum at 60°C. The product (0.54 g) was a brown-colored powder with reduced absorptions at 3,060 cm–1 (N-H) compared with the PSNH2 starting material. The elemental analysis gave Mg 1.83 mmol/g.

Preparation of (S,S,S,R,R,R)-(CH3CHC(O)O)6 and Na[(S,S,S,S,S,S)-(CH3CHC(O)O)6]2BPh4•CHCl3.

 (i) (S,S,S,R,R,R)-(CH3CHC(O)O)6: To the CH3CN (20 ml) suspension of [(CH3CHC(O)O)6]0.83NaBPh4 ( 2.01 g, 2.87 mmol) was added N,N,N',N'-tetramethylethylenediamine (TMEDA) (3.0 ml, 20 mmol), and the reaction mixture was stirred at 60°C for 6 h. After filtration, the filtrate was evaporated to give a brown, sticky solid. The solid was extracted with CHCl3 (fifteen times, 2 ml). The CHCl3 solution was then concentrated and passed through a SiO2 column by using CHCl3 as elutant to give a colorless solid (0.015 g, 1.2%). Crystallographic quality crystals were obtained by recrystallization in CHCl3. 1H NMR d(CDCl3) 5.43 (q, 2H, CHMe), 5.34 (q, 2H, CHMe), 5.13 (q, 2H, CHMe), 1.64 (d, 6H, Me), 1.54 (d, 6H, Me), 1.52 (d, 6H, Me).

(ii) Na[(S,S,S,S,S,S)-(CH3CHC(O)O)6]2BPh4•CHCl3: The SiO2 gel column was washed with CH3CN (30 ml), and the solution was evaporated. The remaining sticky solid was extracted by CHCl3 and filtered off, and the CHCl3 solution was evaporated to give a yellow solid. The solid was recrystallized to give colorless crystallographic-quality crystals, and 1H NMR and x-ray crystallography showed the chemical formula of Na[(S,S,S,S,S,S)-(CH3CHC(O)O)6]2BPh4•CHCl3 (0.095 g, 5.0%, based on A6 rings). 1H NMR d(CDCl3) 7.42 (broad, 8H, CH = C-H), 7.05 (t, 8H, CH = C-H), 6.88 (t, 4H, CH = C-H), 5.30 (q, 12H, CHMe), 1.56 (d, 36H, CH3); 13C NMR d(CDCl3) 168.4 (C = O), 128.7, 128.3, 127.9, 127.2 (C6H5), 69.2 (CH), 16.9 (CH3).

Preparation of Cyclic Oligolactide by Using PS Amino Magnesium Catalyst (PS-C6H4CH2NHMgCH3).

PS amino magnesium [PS-C6H4CH2NHMgCH3; 0.20 g, 0.32 mmol] and L-lactide (0.43 g, 3.0 mmol) were mixed together. Benzene (20 ml) was added, and the mixture was stirred at 70°C for 4 h. The resin was then filtered off and washed with benzene (two times, 10 ml). The combined filtrate and washings were evaporated to give a colorless, wax-like solid (0.26 g). 1H NMR spectrum showed that it contained 80% oligomers (total yield 47%). The solid was dissolved in methanol and applied in ESI-MS, showing 100% cyclic oligolactide present.

Preparation of Cyclic Oligolactide by Using PS Amino Zinc Catalyst (PS-C6H4CH2NHMgCH3).

PS amino zinc [PS-C6H4CH2NHZnEt; 0.20 g, 0.32 mmol] and L-lactide (0.43 g, 3.0 mmol) were mixed together. Benzene (20 ml) was added, and the mixture was stirred at 70°C for 4 h. The resin was then filtered off and washed with benzene (two times, 10 ml). The combined filtrate and washings were evaporated to give a white solid (0.11 g). 1H NMR spectrum showed that it contained 53% oligomers (total yield 14%). The solid was dissolved in methanol and applied in ESI-MS, showing 100% cyclic oligolactide present.

Preparation of Cyclodepsipeptides by Using PS Amino Lithium Catalyst [PS-C6H4CH2NHLi•(BuLi)x] and (3S,6S)-3-isopropyl-6-methyl-2,5-morpholinedione.

 (i) PS amino lithium [PS-C6H4CH2NHLi•(BuLi)x; 0.65 g, 1.02 mmol] and (3S,6S)-3-isopropyl-6-methyl-2,5-morpholinedione (1.72 g, 10.1 mmol) were mixed together. Benzene (50 ml) was added, and the mixture was stirred at room temperature for 40 h. The beads were then filtered off and washed with benzene (two times, 10 ml). The combined filtrate and washings were evaporated, redissolved in CHCl3, and after passing through the preparative GPC column gave a colorless, amorphous solid (0.34 g, 20%). 1H NMR d(CDCl3) 6.97~7.75 (broad, 1H, NH), 4.98~5.41 [broad, 1H, CH(CH3)-O], 3.81~4.46 [broad, 1H, CH(CH(CH3)2)-NH], 1.26~1.54 [broad, 1H, CH(CH3)2], 0.994 [s, 6H, CH(CH3)2]; 13C NMR d(CDCl3) 170.8~172.5 [O-C(O)], 169.7 [N-C(O)], 69.7~71.3 [CH(CH3)-O], 58.4~59.7 [CH(CH(CH3)2)-NH], 29.1~29.8 [CH(CH3)2], 18.6~19.4, 17.3~17.8 [CH(CH3)2].

(ii) The resin from experiment i was recovered, and (3S,6S)-3-isopropyl-6- methyl-2,5-morpholinedione (1.54 g, 9.0 mmol) was added with benzene (50 ml). The suspension was stirred at room temperature for 40 h. The resin was then filtered and washed with benzene (two times, 10 ml). The combined filtrate and washings were evaporated and passed through the GPC column again and gave a colorless, wax-like solid (0.76 g, 49%).

(iii) Repeating step ii gave equivalent results.

Preparative GPC was applied over the 0.76 g of the cyclodepsipeptides prepared above to give 0.015 g of (AB)4, from which was crystallized the cyclic 3-isopropyl-6-methyl-2,5-morphylinedione tetramer shown in Fig. 7.

Preparation of Cyclodepsipeptides by Using PS Amino Lithium Catalyst [PS- C6H4CH2NHLi•(BuLi)x] and (3S,6S)-3-isobutyl-6-methyl-2,5-morpholinedione.

PS amino lithium [PS-C6H4CH2NHLi•(BuLi)x; 0.34 g, 0.54 mmol] and (3S,6S)-3-isobutyl-6-methyl-2,5-morpholinedione (1.00 g, 5.4 mmol) were mixed together. Benzene (30 ml) was added, and the mixture was stirred at room temperature for 16 h. The beads were then filtered off and washed with benzene (two times, 10 ml). The combined filtrate and washings were evaporated, redissolved in CHCl3, and after passing through the preparative GPC column gave a colorless, amorphous solid (0.58 g, 58%). 1H NMR d(CDCl3) 7.29~8.05 (broad, 1H, NH), 4.89~5.39 [broad, 1H, CH(CH3)-O], 4.01~4.56 [broad, 1H, CH(CH2CH(CH3)2)-NH], 1.58~1.99 (broad, 2H, CH2-CH), 1.20~1.53 [broad, 1H, CH(CH3)2], 0.87~0.98 [s, 6H, CH(CH3)2]; 13C NMR d(CDCl3) 170.7~173.9 (C = O), 69.5~71.6 [CH(CH3)-O], 51.6~52.7 (CH-N), 38.4~39.1 (CH2), 24.7~25.1 [CH(CH3)2], 22.9, 22.1~22.5, 21.0, 17.3~17.6 [CH(CH3)2].

Preparation of Cyclodepsipeptides by Using PS Amino Lithium Catalyst [PS- C6H4CH2NHLi•(BuLi)x] and (3S,6S)-3,6-dimethyl-2,5-morpholinedione.

PS amino lithium [PS-C6H4CH2NHLi•(BuLi)x; 0.34 g, 0.54 mmol] and (3S,6S)-3,6-dimethyl-2,5-morpholinedione (0.80 g, 5.4 mmol) were mixed together. Benzene (15 ml) was added and the mixture was stirred at room temperature for 10 h. The beads were then filtered off, washed with benzene (two times, 10 ml), resuspended in benzene (20 ml), and heated at 60°C for 10 h. The mixture was filtered, and the solids were washed with benzene (two times, 5 ml). The last filtrate and washings were combined, and benzene was removed under vacuum. Redissolving in CHCl3 and passing through the preparative GPC column gave a colorless, amorphous solid (0.31 g, 39%). 1H NMR d(CDCl3) 7.46~8.04 (broad, 1H, NH), 4.88~5.37 [broad, 1H, CH(CH3)-O], 4.07~4.49 [broad, 1H, CH(CH3)-NH], 1.21~1.56 (broad, 6H, CH3); 13C NMR d(CDCl3) 170.7~173.0 [O-C(O)], 70.0~71.3 [CH(CH3)-O], 48.8~49.5 [CH(CH3)-NH], 17.2~17.6, 15.5~16.3 (CH3).

Preparation of Cyclodepsipeptides by Using PS Amino Lithium Catalyst [PS- C6H4CH2NHLi•(BuLi)x] and (3S,6S)-3-benzyl-6-methyl-2,5-morpholinedione.

PS amino lithium [PS-C6H4CH2NHLi•(BuLi)x; 0.34 g, 0.54 mmol] and (3S,6S)-3-benzyl-6-methyl-2,5-morpholinedione (1.19 g, 5.4 mmol) were mixed together. Benzene (25 ml) was added, and the mixture was stirred at room temperature for 10 h. The beads were then filtered off, washed with benzene (two times, 10 ml), resuspended in benzene (25 ml), and heated at 60°C for 10 h. The mixture was filtered, and the beads were washed with benzene (two times, 5 ml). The last filtrates and washings were combined, and the solids obtained upon removal of the benzene were redissolved in CHCl3 and passed through the preparative GPC column to give a colorless, amorphous solid (0.40 g, 34%). 1H NMR d(CDCl3) 6.84~8.21 (broad, 1H, NH), 7.10~7.31 (m, 5H, C6H5), 4.80~5.51 [broad, 1H, CH(CH3)], 2.93~4.71 [broad, 1H, CH(CH2C6H5)], 2.93~3.44 (broad, 2H, CH2), 0.88~1.56 (broad, 3H, CH3); 13C NMR d(CDCl3) 172.7, 172.4, 172.3, 172.0, 171.4, 170.9, 170.4, 170.2, 170.0, 169.9, 169.7, 169.1 (C = O), 128.4~129.3, 126.7~127.5 (C6H5), 72.1, 71.9, 71.7, 71.6, 71.1, 70.9, 70.6, 70.4, 69.9 [CH(CH3)], 54.8, 54.4, 53.9, 53.3, 53.1 [CH(CH2C6H5], 37.1, 36.7, 36.3, 36.2, 35.8, 35.7, 35.6, 35.5 (CH2), 18.1, 17.8, 17.7, 17.6, 17.5, 17.4, 17.2, 16.8~17.1, 15.6 (CH3).