Reaction SMILES: [CH2:1]([CH:4]1[CH:30]=[C:29]([CH3:31])[CH2:28][CH:27]([CH3:32])[CH2:26][CH:25]([O:33][CH3:34])[CH:24]2[O:35][C:20]([OH:39])([CH:21]([CH3:38])[CH2:22][CH:23]2[O:36][CH3:37])[C:19](=[O:40])[C:18](=[O:41])[N:17]2[CH:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[C:11](=[O:42])[O:10][CH:9]([C:43]([CH3:54])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([OH:51])[CH:47]([O:52][CH3:53])[CH2:46]2)[CH:8]([CH3:55])[CH:7]([OH:56])[CH2:6][C:5]1=[O:57])[CH:2]=[CH2:3].C([Si](C1C=CC=CC=1)(C1C=CC=CC=1)[O:63][C:64](=[O:74])[CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][C:71](O)=[O:72])(C)(C)C.Cl.CN(C)CCCN=C=NCC.F>ClCCl.CN(C)C1C=CN=CC=1.C(#N)C.C1C=CC=CC=1>[CH2:1]([CH:4]1[CH:30]=[C:29]([CH3:31])[CH2:28][CH:27]([CH3:32])[CH2:26][CH:25]([O:33][CH3:34])[CH:24]2[O:35][C:20]([OH:39])([CH:21]([CH3:38])[CH2:22][CH:23]2[O:36][CH3:37])[C:19](=[O:40])[C:18](=[O:41])[N:17]2[CH:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[C:11](=[O:42])[O:10][CH:9]([C:43]([CH3:54])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([O:51][C:71](=[O:72])[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65][C:64]([OH:74])=[O:63])[CH:47]([O:52][CH3:53])[CH2:46]2)[CH:8]([CH3:55])[CH:7]([OH:56])[CH2:6][C:5]1=[O:57])[CH:2]=[CH2:3]
Reactant: C=CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Reactant: CC(C)(C)[Si](OC(=O)CCCCCCC(=O)O)(c1ccccc1)c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CC#N
Solvent: c1ccccc1
Product: C=CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(OC(=O)CCCCCCC(=O)O)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Reaction time: 1.5 h

Procedure:
17-allyl-1,14-di-hydroxy-12-[2-(4-hydroxy-3-methoxy-cyclohexyl)-1-methyl-vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9] octacos-18-ene-2,3,10,16-tetraone (FK-506, 1, 3.3 mg, 4.10 μmol) was twice boiled together with benzene, and dissolved in dichloromethane (39 μl), and 16.2 μl (4.09 μmol) of a solution of O-mono(tert-butyl-diphenyl-silanyl)octanedioic acid in dichloromethane (100 mg/ml) was added. After this was dissolved by the addition of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (WSC/HCl, 0.94 mg, 4.90 μmol) and 23 μl (1.88 μmol) of a solution of 4-dimethylaminopyridine in dichloromethane (10 mg/ml) at room temperature, the solution was allowed to stand for 1.5 hours. This solution was extracted by the addition of dichloromethane (150 μl) and saturated aqueous sodium carbonate (150 μl). The organic phase collected was concentrated by blowing a nitrogen stream. After the syrup obtained was dissolved by the addition of acetonitrile (28 μl), 46-48% aqueous hydrogen fluoride (6.5 μl) was added at room temperature, and the solution was allowed to stand for 1.5 hours. This solution was extracted by the addition of ethyl acetate (100 μl) and saturated aqueous sodium carbonate (100 μl), and the organic phase was concentrated by blowing a nitrogen stream, to yield a syrup of mixture A. The mixture A was used as is without purification and the like in the next step. The mixture A was used while no structural information was available about whether or not the mixture A contains a compound having the spacer introduced thereto only at a position where the binding to FKBP12 is not affected, for example, 17-allyl-1,14-di-hydroxy-12-{2-[4-(7-carboxy-heptanoyl-oxy)-3-methoxy-cyclohexyl]-1-methyl-vinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone shown in Reference Production Example 2, or contains FK506 having the spacer introduced therein at a position where there is a contribution to the binding to FKBP12, or contains FK506 having a plurality of spacers introduced thereto, and the like.