The crude earthworm extract catalysed direct asymmetric aldol reactionsa.

aOptimized reaction conditions: aldehyde (0.50 mmol), ketone (7.50 mmol), the crude earthworm extract (75 mg), deionized water (0.05 mL), and MeCN (0.95 mL) at 25°C.bYield of the isolated product after silica gel chromatography.cDetermined by chiral HPLC analysis performed using Chiralpak AD-H, AS-H, or Chiralcel OD-H column, by comparing the retention time with those of known compounds (For details, please see the Supplementary material).dUn-optimized conditions: 4-cyanobenzaldehyde (0.50 mmol), cyclohexanone (2.50 mmol), the crude earthworm extract (50 mg), deionized water (0.05 mL), and MeCN (0.95 mL) at 30°C.eThe reaction was conducted in the absence of the crude earthworm extract, otherwise under the same conditions as entry 9.fThe crude earthworm extract (50 mg) in deionized water (3 mL) was stirred at 100°C for 24 h, and then water was removed under reduced pressure before use. The reaction was conducted under the same conditions as entry 9.gThe crude earthworm extract (50 mg) in Cu2+ solution (0.25 M) [anhydrous CuSO4 (120 mg) in deionized water (3 mL)] was stirred at 30°C for 24 h, and then water was removed under reduced pressure before use. The reaction was conducted under the same conditions as entry 9.hThe reaction was conducted using anhydrous CuSO4 (120 mg) as a catalyst instead of the crude earthworm extract, otherwise under the same conditions as entry 9.a. 优化后的反应条件：醛（0.50 mmol）、酮（7.50 mmol）、粗蚯蚓提取物（75 mg）、去离子水（0.05 mL）及乙腈（MeCN，0.95 mL）于25℃下反应。b. 经硅胶柱层析分离得到的目标产物的分离收率。c. 采用Chiralpak AD-H、AS-H或Chiralcel OD-H色谱柱进行手性高效液相色谱（chiral HPLC）分析，通过与已知化合物的保留时间比对确定对映体组成，详细内容参见补充材料。d. 未优化的反应条件：4-氰基苯甲醛（0.50 mmol）、环己酮（2.50 mmol）、粗蚯蚓提取物（50 mg）、去离子水（0.05 mL）及乙腈（MeCN，0.95 mL）于30℃下反应。e. 该反应未添加粗蚯蚓提取物，其余反应条件与条目9完全一致。f. 将粗蚯蚓提取物（50 mg）置于去离子水（3 mL）中，于100℃搅拌24 h，随后减压除去水后待用，反应条件与条目9完全一致。g. 将粗蚯蚓提取物（50 mg）置于0.25 M Cu²+溶液（由无水硫酸铜120 mg溶于去离子水3 mL制得）中，于30℃搅拌24 h，随后减压除去水后待用，反应条件与条目9完全一致。h. 该反应以无水硫酸铜（120 mg）作为催化剂替代粗蚯蚓提取物，其余反应条件与条目9完全一致。