Syntheses of naturally occurring cytotoxic [7.7]paracyclophanes, (-)-cylindrocyclophane A and its enantiomer, and implications for biological activity.
The total syntheses of (-)-cylindrocyclophane A (1), a naturally occurring, cytotoxic [7.7]paracyclophane, and its enantiomer have been achieved in an enantiodivergent manner starting from a chiral propargyl alcohol building block using Smith's cross metathesis/ring-closing metathesis protocol as the key step. The biological evaluation of both enantiomers of cylindrocyclophane A (1 and ent-1) and its analogues indicated that the chirality of 1 is irrelevant to its cytotoxicity, which is attributed to the resorcinol motifs embedded in the robust [7.7]paracyclophane framework.
Yamakoshi
Hiroyuki
H
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aobayama, Sendai, Japan.
Ikarashi
Fumiya
F
Minami
Masataka
M
Shibuya
Masatoshi
M
Sugahara
Tsutomu
T
Kanoh
Naoki
N
Ohori
Hisatsugu
H
Shibata
Hiroyuki
H
Iwabuchi
Yoshiharu
Y
D000438:Alcohols / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation; D045325:HCT116 Cells; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C544518:(7.7)paracyclophane; D000438:Alcohols; D000970:Antineoplastic Agents; D001688:Biological Products; D011084:Polycyclic Aromatic Hydrocarbons; D011083:Polycyclic Compounds; C434087:cylindrocyclophane A