Citation: Shi Feng, Li-Fei Cui, He-Geng Wei, Guo-Jun Zheng, Ya-Ping Wang, Xiang-Jing Wang, Ji Zhang, Wen-Sheng Xiang. Improved and efficient synthesis of Maxacalcitol[J]. Chinese Chemical Letters, ;2014, 25(05): 771-774. doi: 10.1016/j.cclet.2014.03.001 shu

Improved and efficient synthesis of Maxacalcitol

1.
a College of Science, Northeast Agricultural University, Harbin 150030, China;
2.
b School of Life Science, Northeast Agricultural University, Harbin 150030, China;
3.
c Harbin FRP Institute, Harbin 150036, China;
d Zhejiang Hisun Pharmaceutical Co.
d Zhejiang Hisun Pharmaceutical Co., Ltd., Taizhou 318000, China

Corresponding author: Wen-Sheng Xiang,
Received Date: 18 December 2013
Available Online: 20 February 2014

Maxacalcitol, the 22-oxa-derivative of 1α, 25-dihydroxyvitamin D₃, has been used as an antihyperparathyroidism and antipsoriatic drug. In this paper, an alternative synthetic route has been developed using commercially available vitamin D₂ as the starting material. In addition, as a key intermediate, the asymmetric synthesis of 20(S)-alcohol 14 with the chiral auxiliary (R-CBS) was described for the first time. This new synthetic route afforded Maxacalcitol with improved overall yield (13.9%) in eleven steps.
- Vitamin D₃ derivative,
- Maxacalcitol,
- Synthesis,
- Asymmetric reduction
1. [1]
  [1] G. Jones, Vitamin D analogs, Endocrin. Metab. Clin. 39 (2010) 447-472.
2. [2]
  [2] G.H. Posner, M. Kahraman, Organic chemistry of vitamin D analogues, Eur. J. Org. Chem. 24 (2003) 3889-3895.
3. [3]
  [3] A.J. Brown, Vitamin D analogs for the treatment of secondary hyperparathyroidism in chronic renal failure, in: T. Naveh-Many (Ed.), Molecular Biology of the Parathyroid, Kluwer Academic/Plenum Publishers, Austin, USA, 2005, pp. 95-112.
4. [4]
  [4] Y. Nishii, T. Okano, History of the development of new vitamin D analogs: studies on 22-oxacalcitriol (OCT) and 2β-(3-hydroxypropoxy) calcitriol (ED-71), Steroids 66 (2001) 137-146.
5. [5]
  [5] N.C. Harvey, K. Javaid, N. Bishop, et al., MAVIDOS maternal vitamin D osteoporosis study: study protocol for a randomized controlled trial. The MAVIDOS study group, Trials 13 (2012) 13.
6. [6]
  [6] A.J. Brown, E. Slatopolsky, Vitamin D analogs: therapeutic applications and mechanisms for selectivity, Mol. Aspects Med. 29 (2008) 433-452.
7. [7]
  [7] S. Hatakeyama, T. Okano, J. Maeyama, et al., Synthesis and evaluation of 1a 25- dihydroxy-22-oxavitamin D₃(OCT), Bioorg. Med. Chem. 9 (2001) 403-415.
8. [8]
  [8] Y. Fall, V. González, B. Vidal, et al., Stereoselective synthesis of 22-oxacalcitriol (OCT) and analogues modified at C25, Tetrahedron Lett. 43 (2002) 427-429.
9. [9]
  [9] E. Murayama, K. Miyamoto, N. Kubodera, et al., Synthetic studies of vitamin D₃ analogs VⅢ: synthesis of 22-oxavitamin D₃ analogs, Chem. Pharm. Bull. (Tokyo) 34 (1986) 4410-4413.
10. [10]
  [10] N. Kubodera, H. Watanabe, T. Kawanishi, et al., Synthetic studies of vitamin D analogues XI: synthesis and differentiation-inducing activity of 1α, 25-dihydroxy- 22-oxavitamin D₃ analogues, Chem. Pharm. Bull. (Tokyo) 40 (1992) 1494-1499.
11. [11]
  [11] T. Mikami, T. Iwaoka, M. Kato, et al., Practical formation of γ-keto or γ-hydroxy ether linkage from alcohol, Synth. Commun. 27 (1997) 2363-2369.
12. [12]
  [12] M.J. Calverley, Synthesis of MC 903 a biologically active vitamin D metabolite analogue, Tetrahedron 43 (1987) 4609-4619.
13. [13]
  [13] K.L. Perlman, H.M. Darwish, H.F. Deluca, 20-Oxopregnacalciferols: vitamin D compounds that bind the progesterone receptor, Tetrahedron Lett. 35 (1994) 2295-2298.
14. [14]
  [14] S. Anchel, W. Koby, R.G. Michal, et al., Polymorphs of Maxacalcitol and process for the preparation of Maxacalcitol, WO 2012/122451 A2 (2012).
15. [15]
  [15] R. Rodriguez, A.S. Chapelon, C. Ollivier, et al., Stereoselective synthesis of CD-ring precursors of vitamin D derivatives, Tetrahedron 65 (2009) 7001-7015.
16. [16]
  [16] H. Shimizu, K. Shimizu, N. Kuboru, et al., Efficient modification of steroid 20Shydroxy functionality for industrial preparation of 1a,25-dihydroxy-22-oxavitamin D₃, Maxacalcitol, Tetrahedron Lett. 45 (2004) 1347-1350.
17. [17]
  [17] H. Shimizu, K. Shimizu, N. Kubodera, et al., Industrial synthesis of Maxacalcitol, the antihyperparathyroidism and antipsoriatic vitamin D₃ analogue exhibiting low calcemic activity, Org. Process Res. Dev. 9 (2005) 278-287.
18. [18]
  [18] B.G. Anderson, W.E. Bauta, W.R. Cantrell, Development of an improved process for doxercalciferol via a continuous photochemical reaction, Org. Process Res. Dev. 16 (2012) 967-975.
19. [19]
  [19] L.D. Coutts, W.B. Geiss, B.T. Gregg, et al., A stereospecific synthesis of 24(S)- hydroxyvitamin D2, a prodrug for 1a,24(S)-dihydroxyvitamin D₂, Org. Process Res. Dev. 6 (2002) 246-255.
1. [1]
  Yulong Shi , Fenbei Chen , Mengyuan Wu , Xin Zhang , Runze Meng , Kun Wang , Yan Wang , Yuheng Mei , Qionglu Duan , Yinghong Li , Rongmei Gao , Yuhuan Li , Hongbin Deng , Jiandong Jiang , Yanxiang Wang , Danqing Song . Chemical construction and anti-HCoV-OC43 evaluation of novel 10,12-disubstituted aloperine derivatives as dual cofactor inhibitors of TMPRSS2 and SR-B1. Chinese Chemical Letters, 2024, 35(5): 108792-. doi: 10.1016/j.cclet.2023.108792
2. [2]
  Huiju Cao , Lei Shi . sp¹-Hybridized linear and cyclic carbon chain. Chinese Chemical Letters, 2025, 36(4): 110466-. doi: 10.1016/j.cclet.2024.110466
3. [3]
  Pan Hu , Xiaofan Wu , Yi An , Xianjing Zheng , Liang Gao , Yuan Tao , Yajiao Zhang , Zedu Huang , Fener Chen . Batch and continuous-flow asymmetric synthesis of D-pantothenic acid precursor enabled by immobilized ketoreductase mutant. Chinese Chemical Letters, 2026, 37(2): 111945-. doi: 10.1016/j.cclet.2025.111945
4. [4]
  Xinyi Zhang , Kai Ren , Yanning Liu , Zhenyi Gu , Zhixiong Huang , Shuohang Zheng , Xiaotong Wang , Jinzhi Guo , Igor V. Zatovsky , Junming Cao , Xinglong Wu . Progress on Entropy Production Engineering for Electrochemical Catalysis. Acta Physico-Chimica Sinica, 2024, 40(7): 2307057-0. doi: 10.3866/PKU.WHXB202307057
5. [5]
  Lei Feng , Ze-Min Zhu , Ying Yang , Zongbin He , Jiafeng Zou , Man-Bo Li , Yan Zhao , Zhikun Wu . Long-Pursued Structure of Au₂₃(S-Adm)₁₆ and the Unexpected Doping Effects. Acta Physico-Chimica Sinica, 2024, 40(5): 2305029-0. doi: 10.3866/PKU.WHXB202305029
6. [6]
  Ying Chen , Ronghua Yan , Weiyan Yin . Research Progress on the Synthesis of Metal Single-Atom Catalysts and Their Applications in Electrocatalytic Hydrogen Evolution Reactions. University Chemistry, 2025, 40(9): 344-353. doi: 10.12461/PKU.DXHX202503066
7. [7]
  Jiaming Xu , Yu Xiang , Weisheng Lin , Zhiwei Miao . Research Progress in the Synthesis of Cyclic Organic Compounds Using Bimetallic Relay Catalytic Strategies. University Chemistry, 2024, 39(3): 239-257. doi: 10.3866/PKU.DXHX202309093
8. [8]
  Long Jin , Jian Han , Dongmei Fang , Min Wang , Jian Liao . Pd-catalyzed asymmetric carbonyl alkynylation: Synthesis of axial chiral ynones. Chinese Chemical Letters, 2024, 35(6): 109212-. doi: 10.1016/j.cclet.2023.109212
9. [9]
  Tengfei Xuan , Yuan Pan , Zhenyu Shi , Yang Wang . Organocatalytic asymmetric synthesis of oxazolines from N-acylimines. Chinese Chemical Letters, 2025, 36(6): 110352-. doi: 10.1016/j.cclet.2024.110352
10. [10]
  Xiang Huang , Dongzhen Xu , Yang Liu , Xia Huang , Yangfan Wu , Dongmei Fang , Bing Xia , Wei Jiao , Jian Liao , Min Wang . Asymmetric synthesis of difluorinated α-quaternary amino acids (DFAAs) via Cu-catalyzed difluorobenzylation of aldimine esters. Chinese Chemical Letters, 2024, 35(12): 109665-. doi: 10.1016/j.cclet.2024.109665
11. [11]
  Wen-Rui Li , Ru-Bing Wang , Huiqiang Wang , Jin-Yao Yong , Yu-Huan Li , Shi-Shan Yu , Shuang-Gang Ma . Ring-reorganization strategy for asymmetric synthesis of sesquiterpenoid illihenin A and its antiviral activity evaluation. Chinese Chemical Letters, 2025, 36(11): 110945-. doi: 10.1016/j.cclet.2025.110945
12. [12]
  Liyong Ding , Zhenhua Pan , Qian Wang . 2D photocatalysts for hydrogen peroxide synthesis. Chinese Chemical Letters, 2024, 35(12): 110125-. doi: 10.1016/j.cclet.2024.110125
13. [13]
  Xiuhua Wang , Jianrong Steve Zhou . A dicationic nickel complex-catalyzed asymmetric synthesis of chiral benzylic amines: Evolution from reductive amination to borrowing hydrogen reaction. Chinese Chemical Letters, 2026, 37(2): 111148-. doi: 10.1016/j.cclet.2025.111148
14. [14]
  Qi Zhang , Bin Han , Yucheng Jin , Mingrun Li , Enhui Zhang , Jianzhuang Jiang . 2D and 3D phthalocyanine covalent organic frameworks for electrocatalytic carbon dioxide reduction. Chinese Chemical Letters, 2025, 36(9): 110330-. doi: 10.1016/j.cclet.2024.110330
15. [15]
  Xiaoxia WANG , Ya'nan GUO , Feng SU , Chun HAN , Long SUN . Synthesis, structure, and electrocatalytic oxygen reduction reaction properties of metal antimony-based chalcogenide clusters. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1201-1208. doi: 10.11862/CJIC.20230478
16. [16]
  Yihong Li , Zhong Qiu , Lei Huang , Shenghui Shen , Ping Liu , Haomiao Zhang , Feng Cao , Xinping He , Jun Zhang , Yang Xia , Xinqi Liang , Chen Wang , Wangjun Wan , Yongqi Zhang , Minghua Chen , Wenkui Zhang , Hui Huang , Yongping Gan , Xinhui Xia . Plasma enhanced reduction method for synthesis of reduced graphene oxide fiber/Si anode with improved performance. Chinese Chemical Letters, 2024, 35(11): 109510-. doi: 10.1016/j.cclet.2024.109510
17. [17]
  Ting Xie , Xun He , Lang He , Kai Dong , Yongchao Yao , Zhengwei Cai , Xuwei Liu , Xiaoya Fan , Tengyue Li , Dongdong Zheng , Shengjun Sun , Luming Li , Wei Chu , Asmaa Farouk , Mohamed S. Hamdy , Chenggang Xu , Qingquan Kong , Xuping Sun . CoSe₂ nanowire array enabled highly efficient electrocatalytic reduction of nitrate for ammonia synthesis. Chinese Chemical Letters, 2024, 35(11): 110005-. doi: 10.1016/j.cclet.2024.110005
18. [18]
  Hong-Rui Li , Xia Kang , Rui Gao , Miao-Miao Shi , Bo Bi , Ze-Yu Chen , Jun-Min Yan . Interfacial interactions of Cu/MnOOH enhance ammonia synthesis from electrochemical nitrate reduction. Chinese Chemical Letters, 2025, 36(2): 109958-. doi: 10.1016/j.cclet.2024.109958
19. [19]
  Jiaqi Ma , Lan Li , Yiming Zhang , Jinjie Qian , Xusheng Wang . Covalent organic frameworks: Synthesis, structures, characterizations and progress of photocatalytic reduction of CO2. Chinese Journal of Structural Chemistry, 2024, 43(12): 100466-100466. doi: 10.1016/j.cjsc.2024.100466
20. [20]
  Xinyuan Li , Zhuozhu Li , Wenzhong Huang , Jiantao Li , Wei Zhang , Shihao Feng , Hao Fan , Zhuo Chen , Sungsik Lee , Congcong Cai , Liang Zhou . Solvent-free synthesis of Co single atom and nanocluster decorated N-doped carbon for efficient oxygen reduction. Chinese Chemical Letters, 2025, 36(9): 110716-. doi: 10.1016/j.cclet.2024.110716

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(1326)
HTML views(33)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142