11-oxo-olenolic acid [I] 및 유도체를 합성하고 이 화합물들의 corticoid-$5{eta}$-reductase 저해활성과 항염증 활성을 연구하였다. [I]을 $CH_2N_2$로 메칠화하여 11-oxo-oleanolic acid methylester [II] $C_{31}H_{48}O_4$, mp $196{sim}198^{circ}$를 얻었고, oleanolic acid를 $CrO_3$-pyridine으로 산화하여 3-oxo-oleanolic acid [III] $C_{30}H_{46}O_3$, $198{sim}202^{circ}$를 얻고 [III]을 다시 $CrO_3$-초산으로 산화하여 3, 11-dioxo-olenolic acid [IV] $C_{30}H_{44}O_4$, mp $268{sim}270^{circ}$, UV (${lambda}max$) 252nm와 부산물로 3, 11-dioxo-oleanolic acid lactone [V] $C_{30}H_{44}O_4$, mp $265{sim}267^{circ}$를 얻었다. [IV]는 [I]에 비하여 corticoid-$5{eta}$-reductase를 강력히 저해하며 $K_i$값은 [IV]가 $4.2{ imes}10^{-4}M$, [I]이 $4.6{ imes}10^{-4}M$로 측정되었다. 이 화합물의 항염증 작용을 흰쥐의 카라게닌 유발부종시험법으로 측정한 결과 30mg/kg.s.c. 용량에서 hydrocortisone이 66% 부종을 억제한데 비하여 [I]은 63%, [II]는 78% [IV]는 70%, [V]는 66% 억제하였다. 이상의 연구결과로부터 구조와 활성의 관계를 고찰할 때 올레아놀산의 탄소 11 및 12 위치의 $alpha,eta$-unsaturated ketone 구조가 코르티코이드 유사활성에 필수적이며 탄소3위치의 수산기 보다 케톤기가 더 큰활성을 나타나게 하고 C 및 D 환의 락톤 형성에 의한 구조변화는 이 활성증가를 감소시키고 있다. 가장 강한 활성을 나타낸 [II]의 경우는 소수성의 증가에 기인된 것으로 추정된다.
The effect of 11-oxo-oleanlic acid [I] and its derivatives on carrageenin-induced edema in rat kind paw was investigated. The following derivatives were synthesized ; 11-oxo-oleanolic acid methylester [II] $C_{31}H_{48}O_4$ mp $196-198^{circ}$ was derived from [I] by methylation with $CH_2N_2$. 3-Oxo-oleanolic acid [III] $C_{30}H_{46}O_3$, mP $198-202^{circ}$ was obtained from oleanolic acid by $CrO_3$-pyridine oxidation. Oxidation of [III] by $CrO_3$-HAc produced 3, 11-dioxooleanolic acid [IV] $C_{30}H_{44}O_4$, mp $268-270^{circ}$ VU ($lambda$ max) 252 nm and 3, 11-dioxo-oleanolic acid lactone [V] $C_{30}H_{44}O_4$, mp $265-267^{circ}$ as a by-product. [IV] showed strong competitive inhibition against corticoid-$5{eta}$-reductase, $K_i=4.2{ imes}10^{-4}M$, compared to $4.6{ imes}10^{-4}M$ of [I]. The anti-inflammatory activities of 11-oxo-oleanolic acid derivatives were evaluated by rat kind paw carrageenin edema test after s.c, injection with 30mg/kg doses. [I], [II], [IV] and [V] suppressed significantly the edema volumes by 63, 78, 70 and 66%, respectively, compared to 66% of hydrocortisone. The above results suggest that the replacement of OH group in $C_3$ position by ketone group increased the corticomimetic activity, but that the change on the steric structure in C and D rings by lactone formation reduced the activity increase. [II] showed the most powerful activities probably due to increased lipophilicity.
