PT - JOURNAL ARTICLE AU - ATSUSHI KITTAKA AU - HIDEKI HARA AU - MASASHI TAKANO AU - DAISUKE SAWADA AU - MIDORI A. ARAI AU - KENICHIRO TAKAGI AU - TAKAYUKI CHIDA AU - YOSHIFUMI HARADA AU - HIROSHI SAITO AU - KAZUYA TAKENOUCHI AU - SEIICHI ISHIZUKA AU - KEIKO HAYASHI AU - SHINICHI IKUSHIRO AU - TOSHIYUKI SAKAKI AU - TAKAYUKI SUGIURA AU - TAI C. CHEN TI - Synthesis and Biological Activities of 14-<em>epi</em>-MART-10 and 14-<em>epi</em>-MART-11: Implications for Cancer and Osteoporosis Treatment DP - 2009 Sep 01 TA - Anticancer Research PG - 3563--3569 VI - 29 IP - 9 4099 - http://ar.iiarjournals.org/content/29/9/3563.short 4100 - http://ar.iiarjournals.org/content/29/9/3563.full SO - Anticancer Res2009 Sep 01; 29 AB - The 14-epimer of MART-10, namely 14-epi-MART-10 (14-epi-2α-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D3) and its 2-epimeric analog (14-epi-MART-11) were efficiently synthesized using the Julia coupling reaction to connect between the C5 and C6 positions (steroid numbering). An A-ring precursor was prepared from (-)-quinic acid as shown in the previous MART-10 synthesis. The novel 14-epi-CD-ring coupling partner with an elongated two carbon unit as a sulfone was synthesized from 14-epi-25-hydroxy Grundmann's ketone in good yield. The subsequent coupling reaction followed by a deprotection step afforded a mixture of 14-epi-MART-10 and 14-epi-MART-11 in 40% yield. To separate 14-epi-MART-10 and 14-epi-MART-11, each primary hydroxyl group was esterified with a pivaloyl group and the resulting pivalates 2α and 2β were separated by high performance liquid chromatography. After the separation, the C2-stereochemistry of each (2α or 2β) was determined by 1H NMR (nuclear magnetic resonance) studies including NOE (nuclear Overhauser effect) experiments. The pivaloyl group was removed under basic conditions to obtain the target molecules of 14-epi-MART-10 and 14-epi-MART-11, respectively. The VDR (vitamin D receptor)-binding affinity, HL-60 (human promyelocytic leukemia) cell differentiation activity, antiproliferative activity in PZ-HPV-7 (immortalized normal prostate) cells and transactivation activity of the osteocalcin promoter in HOS (human osteoblast cell line) cells (serum-free conditions) were investigated. In addition, the effects on bone mineral density (BMD) and the blood and urine calcium concentrations of ovariectomized (OVX) rats were examined. 14-epi-MART-10 has much greater antiproliferative and cell differentiation activities compared to 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3).