KR910005421B1

KR910005421B1 - Brassinolide analogue

Info

Publication number: KR910005421B1
Application number: KR1019870008039A
Authority: KR
Inventors: 조광연; 허만욱; 김영섭
Original assignee: 재단법인 한국화학연구소; 채영복
Priority date: 1987-07-23
Filing date: 1987-07-23
Publication date: 1991-07-29
Also published as: KR890001922A

Abstract

Brassinolide analogues of formula (I) and (II), useful as a plant growth regulator, are presented. For the prepn. of (I), 6,6- ethylen-2alpha, 3alphaisopropylen-dioxy-5alpha-pregnan-20S-carboxyldehyde is reacted with wittig reagent, and the protecting gp. is removed. The ketone gp. of (I) is reacted with a reducing agent to obtain (II). In the formulas, R= H, C1-10 straigh chain aliphatic gp., C3-10 side chain aliphatic gp., cyclo gp., methylmethylsulfinyl, ethoxymelthyl or aromatic gp. opt. substd. by C1-3 alkyl.

Description

Brassinolide analogues

본 발명은 신규의 브라시노라이드 유사체에 관한 것이다. 특히 본 발명은 식물 생장 조절제로서 유용한 하기 일반식(I) 및 (I')의 브라시노라이드 유사체에 관한 것이다.The present invention relates to novel brassinolide analogs. In particular, the present invention relates to brassinolide analogues of the following general formulas (I) and (I ′) which are useful as plant growth regulators.

상기 식중, R은 수소, 탄소수 1∼10개의 직쇄 지방족기, 탄소수 3∼10개의 측쇄지방족기, 시클로기, 메틸메틸술피닐기, 에톡시메틸기, 1∼3개의 저급알킬기로 치환되어도 좋은 방향족 또는 복소환기를 나타낸다.In the above formula, R is an aromatic or heterocyclic group which may be substituted with hydrogen, a linear aliphatic group having 1 to 10 carbon atoms, a branched aliphatic group having 3 to 10 carbon atoms, a cyclo group, a methylmethylsulfinyl group, an ethoxymethyl group, or a lower alkyl group having 1 to 3 carbon atoms. Indicates ventilation.

상기 일반식(I) 화합물의 기에 대한 설명중, 직쇄 지방족기란 탄소수 1∼10개의 알킬기, 탄소수 2∼10의 알케닐을 의미하며, 측쇄지방족기란, 이소프로필, 이소부틸, 이소펜틸, 이소헥실, 이소헵틸, 이소옥틸, sec-부틸, sec-펜틸, sec-헥실, sec-헵틸, sec-옥틸, ter-아밀, ter-헥실, ter-헵틸, ter-옥틸기를 의미한다. 또한 시클로기란 탄소수 3∼10의 시클로알킬기, 시클로알케닐기, 시클로알킬저급알킬기를 나타내다.In the description of the group of the above general formula (I), the straight chain aliphatic group means an alkyl group having 1 to 10 carbon atoms and an alkenyl having 2 to 10 carbon atoms, and the side chain aliphatic group is isopropyl, isobutyl, isopentyl, isohexyl, Isoheptyl, isooctyl, sec-butyl, sec-pentyl, sec-hexyl, sec-heptyl, sec-octyl, ter-amyl, ter-hexyl, ter-heptyl, ter-octyl group. In addition, a cyclo group represents a C3-C10 cycloalkyl group, a cycloalkenyl group, and a cycloalkyl lower alkyl group.

방향족기란 페닐기, 1∼3개의 저급알킬기가 치환된 페닐기, 벤질기, 1∼3개의 저급알킬기가 치환된 벤질기, 페닐에테닐기, 페닐저급알킬기, 1∼3개의 저급알킬기가 치환된 페닐저급알킬기 등을 나타내며, 1∼3개의 저급알킬기로 치환되어도 좋은 복소환기란 피리딜기, 1∼3개의 저급알킬기로 치환된 피리딜기, 푸라닐기, 1∼3개의 저급알킬기로 치환된 푸라닐기, 푸라닐저급알킬기, 옥사졸기, 이소옥사졸기, 저급알킬기로 치환된 이소옥사졸기, 옥사졸저급알킬기, 티오페닐기, 저급알킬기로 치환된 티오페닐기, 티오페닐저급알킬기, 티오피라닐기 피롤릴기, 피라졸릴기, 피라지닐기, 피리미디닐기, 피리다진일기, 페노티아지닐기 등을 나타낸다.An aromatic group is a phenyl group, a phenyl group substituted with 1 to 3 lower alkyl groups, a benzyl group, a benzyl group substituted with 1 to 3 lower alkyl groups, a phenylethenyl group, a phenyl lower alkyl group and a phenyl lower group substituted with 1 to 3 lower alkyl groups Heterocyclic group which may represent an alkyl group etc. and may be substituted by 1-3 lower alkyl groups is a pyridyl group, the pyridyl group substituted by 1-3 lower alkyl groups, furanyl group, the furanyl group substituted by 1-3 lower alkyl groups, furanyl Lower alkyl group, oxazole group, isoxazole group, isoxazole group substituted with lower alkyl group, oxazole lower alkyl group, thiophenyl group, thiophenyl group substituted with lower alkyl group, thiophenyl lower alkyl group, thiopyranyl group pyrrolyl group, pyrazolyl group, A pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a phenothiazinyl group, etc. are shown.

하기 일반식(A)의 브라시노라이드 화합물은 1979년 미국의 클로브 등에 의해 유채의 화분으로부터 처음으로 분리된 화합물로서(Nature, 281, 216, 1979) 식물 생육 촉진물질이며, 이는 1980년 풍등이 입체 선택적으로 합성했다[J. Am. Chem. Soc., 102, 6580(1980)]The brassinolide compound of the following general formula (A) is a compound which was first isolated from pollen of rapeseed by the US Clove et al. In 1979 (Nature, 281, 216, 1979), and is a plant growth promoting material. Selectively synthesized [J. Am. Chem. Soc., 102, 6580 (1980)].

그후, 이 화합물이 식물의 생장에 미치는 효과가 여러면에서 검토되었다(Chem. ＆ Eng. News, Nov. 5, 20, 1979) 브라시노라이드는 강력한 식물 생장 촉진 효과를 갖는다고 보고되어 있으며, 이는 식물 세포의 길이 생장과 세포분열의 촉진에 의한 것으로 밝혀졌다. 이들 물질은 극히 낮은 농도(1×10^-4μg/ml)에서도 효과가 있다고 보고되어 왔다.[Agric. Bio. Chem, 48(3), 719-726, 1984, ibid 47(5), 1139-1141, 1983].Thereafter, the effect of this compound on plant growth has been reviewed in many ways (Chem. & Eng. News, Nov. 5, 20, 1979). Brassinolides have been reported to have potent plant growth promoting effects. It has been shown that the length of plant cells is due to the growth and division of cells. These substances have been reported to be effective at extremely low concentrations (1 × 10 ⁻⁴ μg / ml). [Agric. Bio. Chem, 48 (3), 719-726, 1984, ibid 47 (5), 1139-1141, 1983].

현재 이런 종류의 화합물들을 농업에 이용하려는 시도가 미국, 일본, 유럽 등에서 널리 행하여지고 있으며, 상당히 성공적인 결과들이 보고되고 있다.Attempts to use these types of compounds in agriculture are now widely undertaken in the United States, Japan and Europe, and fairly successful results have been reported.

첫번째 시도는 보통식물보다 더 빠르게 꽃이 피고 열매가 맺으며, 빨리 익게하는 시도가 벼, 딸기, 양상치, 대두콩과 보리 등에 행하여 졌으며, 이 시험 결과, 이들 브라시노라이드가 유묘 상태의 식물에 대해, 태양광을 좀더 효과적으로 이행케하는 것으로 믿어지고 있다. 이제 막 싹이 트는 식물체의 약 1에어커의 면적에 1mg정도만 뿌려도 조기 수확등의 목표를 달성할 수 있는 것으로 믿어져, 우리나라, 캐나다. 알래스카와 같은 비교적 북쪽에 위치한 지역에서 수확기를 단축함으로서 생산량을 증대시킬 수 있으며, 비교적 따뜻한 나라에선 1번 더 수확할 수 있는 가능성을 제시한다고 볼 수 있다.The first trials blossomed and fruited faster than ordinary plants, and early ripening attempts were made on rice, strawberries, lettuce, soybeans, and barley. It is believed to make sunlight more efficient. It is believed that we can achieve the goal such as early harvesting even if we just sprinkle about 1mg on approximately 1 acre of sprouting plant, Korea, Canada. In a relatively northerly region such as Alaska, shortening of the harvester can increase yields and, in a relatively warm country, offers the possibility of one more harvest.

둘째로, 브라시노라이드는 식물체가 잡초와 곤충, 질병 그리고 그 외의 여러 불리한 환경적인 요건(서리, 가뭄)에 가장 취약한 시기인 유묘시기에 이를 강하게 하여 주기 때문에, 최종 산물의 상태가 좋고, 더욱 커질 수 있다. 브라시노라이드로 처리할 경우, 뿌리가 굳건해져(예, 딸기, 토마토, 콩에서), 조기 수확 뿐만 아니라, 노화도 늦추어 주는 것으로 믿어지고 있다. 실제 미국 농무성의 연구팀의 연구 결과로는 몇몇 작물에서 약 15%∼20%의 증수가 있었고, 감자의 눈에 발라준 결과 그 크기가 커져 시장에서의 인기가 좋았다고 하며, 콩의 온실 실험에선 32%나 증수가 있었다고 한다.Second, because brassinolide strengthens it during the seedling season, when plants are most vulnerable to weeds, insects, diseases and other adverse environmental requirements (frost, drought), the final product is in good condition and grows larger. Can be. When treated with brassinolide, it is believed that the roots are firm (eg from strawberries, tomatoes and beans), which slow down aging as well as early harvest. In fact, the US Department of Agriculture's research team found that some crops had about 15% to 20% increase, and the size of the potato's eye showed its size and popularity in the market. I said there was some increase.

이 화합물들은 그후 연구 결과[T. Morishita, H. Abe, M. Uchiyama, S. Marumo, S. Takatsuto and N. Ikekawa, Phytochem., 22, 1051(1983) S. Takatsuto, B. Ying, M. Morisaki and N. Ikekawa, J. Chromatogr., 239, 233(1982) M. Ikeda, S. Takatsuto, T. Sassa, N. Ikekawa and M. Nukina, Agric. Biol. Chem., 47, 655(1983) T. Yokota, J. Baba and N. Takahashi, Tetrahedron Lett., 23, 4965(1982) H. Abe, I. Morishita, M. Uchiyama, S. Marumo, K. Munakata, S. Takatsuto and M. Ikekawa, Agric. Biol. Chem., 46, 2609(1982) H. Abe, T. Morishita, M. Uchiyama, S. Takatsuto, N. Ikekawa, M. Ikeda, T. Sassa, T. Kitsuwa and S. Marumo, Experientia, 39, 351(1983) T. Yokota, M. Arima and N. Takahashi, Tetrahedron Lett., 23, 1275(1982) J. Baba, T. Yokota and N. Takahashi, Agric. Biol. Chem., 47. 659(1983) T. Yokoda, J. Baba and N. Takahashi, Agric. Biol. Chem., 47, 1409(1983) T. Yokota, M. Arima, N. Takahashi, S. Takatsuto, N. Ikekawa, T. Takematsu, Agric. Biol. Chem., 47(10), 2419-2420(1983)]에 의하면, 자연계에도 널리 존재하는 것으로 알려져 있으며, 앞으로 농업적인 면에서 광범위한 응용이 기대되고 있는 화합물이다.These compounds were then studied [T. Morishita, H. Abe, M. Uchiyama, S. Marumo, S. Takatsuto and N. Ikekawa, Phytochem., 22, 1051 (1983) S. Takatsuto, B. Ying, M. Morisaki and N. Ikekawa, J. Chromatogr , 239, 233 (1982) M. Ikeda, S. Takatsuto, T. Sassa, N. Ikekawa and M. Nukina, Agric. Biol. Chem., 47, 655 (1983) T. Yokota, J. Baba and N. Takahashi, Tetrahedron Lett., 23, 4965 (1982) H. Abe, I. Morishita, M. Uchiyama, S. Marumo, K. Munakata , S. Takatsuto and M. Ikekawa, Agric. Biol. Chem., 46, 2609 (1982) H. Abe, T. Morishita, M. Uchiyama, S. Takatsuto, N. Ikekawa, M. Ikeda, T. Sassa, T. Kitsuwa and S. Marumo, Experientia, 39, 351 (1983) T. Yokota, M. Arima and N. Takahashi, Tetrahedron Lett., 23, 1275 (1982) J. Baba, T. Yokota and N. Takahashi, Agric. Biol. Chem., 47. 659 (1983) T. Yokoda, J. Baba and N. Takahashi, Agric. Biol. Chem., 47, 1409 (1983) T. Yokota, M. Arima, N. Takahashi, S. Takatsuto, N. Ikekawa, T. Takematsu, Agric. Biol. Chem., 47 (10), 2419-2420 (1983), are widely known to exist in the natural world, and are expected to be widely used in agriculture in the future.

그러나. 이 화합물은, 그 구조에서 알 수 있듯이 7개의 키랄 중심(Chiral Center)을 가지고 있으며, 그 구조가 복잡하여 대량 생산에 문제가 있으며, 자연 상태에서 불안정하여 쉽게 그 효과를 상실하는 결점을 가지고 있다.But. The compound has seven chiral centers, as can be seen in its structure, and its structure is complex, which causes problems in mass production, and is unstable in nature and easily loses its effect.

본 발명자들은 식물에 대해 브라시노라이드와 같은 생리적인 효과를 가지고 있으면서도, 합성이 용이하고, 생산 가격이 저렴한 화합물을 개발하기 위하여, 예의 연구를 한 결과, 브라시노라이드의 측쇄가 생물학적 활성을 좌우하는 중요한 인자임을 발견하였다. 즉 측쇄의 길이가 탄소사슬로 볼때 3개 내지 5개의 범위에 있어야 하며, 적절한 소수성을 갖어야 한다는 것이다.The present inventors have conducted intensive studies to develop compounds that have a physiological effect such as brassinolide on plants, but are easy to synthesize and have low production cost. It was found to be an important factor. That is, the length of the side chain should be in the range of 3 to 5 in terms of carbon chain, and should have appropriate hydrophobicity.

따라서 이의 요구도를 충족하는 여러 화합물들을 제조하였고, 특히 방향족 화합물을 측쇄에 도입한 화합물들도 제조하였다. 이들 화합물에 대해 타미나조인트법으로 실험한 결과, 강력한 생리활성을 가지고 있음을 발견하고 본 발명을 완성하게 되었다.Therefore, several compounds were produced that fulfilled the requirements thereof, and in particular, compounds in which aromatic compounds were introduced into the side chain. As a result of experiments with these compounds by the tamina joint method, it was found that they had strong physiological activity and completed the present invention.

본 발명은 신규의 상기 일반식(I) 브라시노라이드 유사체를 제공하는데 있다.The present invention seeks to provide novel general formula (I) brassinolide analogs.

이하 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.

본 발명의 일반식(I')의 브라시노라이드 유사체는 하기 방법에 의해 제조될 수 있다. 즉 하기 일반식(II)의 6,6-에틸렌-2α,3α-이소프로필렌-디옥시-5α-프레그난-20S-카르복스알데히드를 염기하 워티히(Wittig) 시약과 반응시켜 하기 일반식(III)의 화합물을 얻은 후, 이의 보호기를 제거하여 상기 일반식(I) 브라시노라이드 유사체를 얻거나, 생성된 일반식(I) 화합물의 6위치의 케톤기를 통상의 환원제와 반응시켜 상기 일반식(I')의 브라시노라이드 유사체를 제조한다.Brassinolide analogues of general formula (I ′) of the present invention may be prepared by the following process. That is, 6,6-ethylene-2α, 3α-isopropylene-dioxy-5α-pregnan-20S-carboxaldehyde of the following general formula (II) is reacted with a base-Wittig reagent to give a general formula (II) After obtaining the compound of III), the protecting group thereof is removed to obtain the above general formula (I) brassinolide analogue, or the 6-position ketone group of the compound of general formula (I) is reacted with a conventional reducing agent Prepare the brassinolide analogue of (I ').

상기 식중 R은 전술한 바와 같다. 상기 일반식(II)의 화합물은 하기의 합성 경로에 따라 제조될 수 있다.Wherein R is as described above. The compound of formula (II) may be prepared according to the following synthetic route.

상기 일반식(II) 화합물도 신규하며, 본 발명의 범위에 속한다. 합성 공정중 온도 용매 등에 조건은 절대적인 수치가 아니고 바람직한 조건을 나타냄은 말할 나위도 없다. 상기 합성 경로를 약술하여 명백히 한다.The above general formula (II) compounds are also novel and belong to the scope of the present invention. It goes without saying that the conditions in the temperature solvent and the like during the synthesis process are not absolute numerical values, but represent preferable conditions. The synthetic route is outlined and made clear.

상업적으로 쉽게 구할 수 있는 스티그마스테롤(IV)을 피리딘 속에서 p-톨루엔 술포닐 클로라이드(V)로 반응시켜 스티그마스테롤-3-톨실레이트(V)를 얻는다. 이를 용매화 분해하여 i-스티그마스테롤(VI)을 만든 다음, 피리딘-삼산화크롬으로 산화하여 6-케토화합물(VII)을 얻은 다음 술포란을 용매로 하여 톨루엔술포닐히드록시드로 재배열(rearrangement)시키면 2,22-디엔화합물(VIII)가 얻어진다.Commercially readily available stigmasterol (IV) is reacted with p-toluene sulfonyl chloride (V) in pyridine to give stigmasterol-3-tolsylate (V). This was subjected to solvation to form i-stigmasterol (VI), which was then oxidized to pyridine-chromium trioxide to yield 6-keto compound (VII), followed by rearrangement with toluenesulfonyl hydroxide with sulfolane as solvent. 2,22-diene compound (VIII) is obtained.

이것을 아세톤을 용매로하여 건조 질소하에서 촉매 오스밀화 반응(Osmylation)시키면 2,3-디히드록시-22-엔-5α-스티그마스톤-6-온(IX)이 얻어진다.Catalytic ossylation reaction with acetone as the solvent under dry nitrogen yields 2,3-dihydroxy-22-ene-5α-sigmastone-6-one (IX).

이를 히드록시기와 케톤기 부분을 보호한 후에, 70℃에서 오존으로 2중 결합을 잘러서 상기 출발물질인 알데히드(II)을 얻는다.After protecting the hydroxyl group and the ketone group moiety, the double bond is cut with ozone at 70 ° C. to obtain the starting material aldehyde (II).

본 발명은 상기 일반식(II)의 알데히드를 위티히 시약 즉(C₆H₅)₃PCH₂P

X

와 염기중 실온에서 환류하 반응시키면 상기 일반식(III) 화합물을 얻는다.In the present invention, the aldehyde of the general formula (II) is Wittich reagent, namely (C ₆ H ₅ ) ₃ PCH ₂ P

X

The reaction is carried out under reflux at room temperature in a base to obtain the above general formula (III) compound.

이를 불활성 유기용매중 실온에서 산존재하 반응시켜 6-위치의 보호기를 제거하면 목적하는 일반식(I)의 브라시노라이드 유사체를 얻을 수 있다. 필요에 따라 상기 일반식(I) 화합물을 보란과 같은 환원제와 반응시키면 2α,3α,6α-트리히드록시 브라시노라이드 유사체(I')를 제조할 수 있다.This reaction is carried out in the presence of acid in an inert organic solvent to remove the protecting group at the 6-position to obtain the desired brassinolide analogue of general formula (I). If necessary, the compound of general formula (I) may be reacted with a reducing agent such as borane to prepare 2α, 3α, 6α-trihydroxy bracinolide analog (I ′).

이하 실시예로서 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail with reference to Examples.

[실시예 1]Example 1

스티그마스테릴-3-토실레이트(V)의 제조Preparation of stigmasteryl-3-tosylate (V)

p-톨루엔술포닐클로라이드(18.0gr)을 건조 피리딘(200ml)에 녹인 스티그마스테롤(15.0gr)의 용매에 가한다. 위의 반응 혼합물을 상온의 암실에서 12시간 반응을 시킨 다음, 5%의 중탄산칼륨 수용액 1ℓ에 교반을 시키면서 서서히 붓는다. 이때 생성되는 고형상의 침전물을 여과하고, 침전물에 묻은 피리딘을 제거하기 위해 수회 물로 씻은 다음 감압하 그리고 60℃ 이하에서 건조시킨다. 무수아세톤에서 재결정을 한다. 결정은 흰색이다. 수율은 정량적이다.p-toluenesulfonylchloride (18.0 gr) is added to a solvent of stigmasterol (15.0 gr) dissolved in dry pyridine (200 ml). The reaction mixture was reacted for 12 hours in a dark room at room temperature, and then slowly poured into 1 L of 5% aqueous potassium bicarbonate solution while stirring. The resulting solid precipitate is filtered off, washed several times with water to remove pyridine from the precipitate, and then dried under reduced pressure and below 60 ° C. Recrystallize from anhydrous acetone. The crystal is white. Yield is quantitative.

융점 : 132∼133℃Melting Point: 132 ~ 133 ℃

NMR δ(60MHz, CDCl₃/TMS) : 0.67, 0.73, 0.78, 0.83, 0.87(CH₃), 1.04∼2.40(CH^- ₂, CH^-), 2.42(3H, CH₃-C₆H₄ ^-), 4.0∼4.58(1H, bs), 4.95∼5.18(2H, m), 5.18∼5.43(1H, m), 7.2∼7.92(4H, q, J₁=23Hz, J₂=8Hz) _{NMR δ (60MHz, CDCl 3 /} TMS): 0.67, 0.73, 0.78, 0.83, 0.87 (CH 3), 1.04~2.40 (CH - 2, CH -), 2.42 (3H, CH 3 -C 6 H 4 -) , 4.0 to 4.58 (1H, bs), 4.95 to 5.18 (2H, m), 5.18 to 5.53 (1H, m), 7.2 to 7.92 (4H, q, J ₁ = 23 Hz, J ₂ = 8 Hz)

I.R(KBr-pellet) νmax(cm^-1) : 2930(s), 2840(s), 1695(w), 1495(w), 1465(m), 1440(m), 1390(m), 1370(m), 1360(s), 1320(w), 1305(w), 1298(w), 1270(w), 1200(s), 1180(s), 1143(2), 1125(w), 1105(m), 1025(w), 1015(w), 1000(w), 980(s), 950(s), 938(m), 900(s), 880(s), 878(m), 855(m), 830(s), 810(m), 805(m), 790(w), 755(w), 708(w), 742(w), 708(w), 680(s), 640(w), 600(w), 565(s).IR (KBr-pellet) ν max (cm ^-1 ): 2930 (s), 2840 (s), 1695 (w), 1495 (w), 1465 (m), 1440 (m), 1390 (m), 1370 ( m), 1360 (s), 1320 (w), 1305 (w), 1298 (w), 1270 (w), 1200 (s), 1180 (s), 1143 (2), 1125 (w), 1105 ( m), 1025 (w), 1015 (w), 1000 (w), 980 (s), 950 (s), 938 (m), 900 (s), 880 (s), 878 (m), 855 ( m), 830 (s), 810 (m), 805 (m), 790 (w), 755 (w), 708 (w), 742 (w), 708 (w), 680 (s), 640 ( w), 600 (w), 565 (s).

[실시예 2]Example 2

i-스티그마스테롤의 제조Preparation of i-Stig Masterol

스티그마스테롤-3-토실레이트(5.5gr)와 중탄산칼륨(3.2gr)을 아세톤 (2ℓ)에 녹인 다음, 물(200ml)을 여기에 더한다. 위의 반응 혼합물을 1시간 동안 환류시킨 다음, 아세톤을 약 3시간에 걸쳐서 증류해서 제거한다. 전혀 반응물을 상온으로까지 냉각시킨 후, 에테르로 추출한다. 추출된 유기 용매층을 물, 포화소금물 등으로 순차적으로 씻은 다음, 무수 황산마그네슘으로 건조한다.Dissolve stigmasterol-3-tosylate (5.5 gr) and potassium bicarbonate (3.2 gr) in acetone (2 l), then add water (200 ml) to it. The reaction mixture was refluxed for 1 hour and then the acetone was distilled off over about 3 hours. The reaction is cooled to room temperature at all and then extracted with ether. The extracted organic solvent layer is washed sequentially with water, saturated brine and the like, and then dried over anhydrous magnesium sulfate.

감압하에서 용매를 제거하여 굳기름 상태의 다소 불순한 i-스티그마스테롤이 정량적으로 얻어졌다. 이를 더 이상의 정제화하는 조작이 없이 다음에 쓰여졌다. 왜냐하면 이때의 불순물들이 다음 반응이 끝난 후에 제거될 수 있었기 때문이다. 반응의 진행에 관한 정보를 얻기 위해, 분석용 시료를 컬럼크로마토그래피를 통하여 얻었다. [고형상은 플로리실(florisil), 전개 용매는 석유 에테르와 벤젠을 2 대 3의 비율로 사용]The solvent was removed under reduced pressure to give quantitatively somewhat impure i-Stigmasterol in a solid oil state. It is written next without further refinement. This is because impurities at this time could be removed after the next reaction. In order to obtain information on the progress of the reaction, an analytical sample was obtained by column chromatography. [Solid form uses florisil and developing solvent uses petroleum ether and benzene in a ratio of 2 to 3]

융점 : 50∼53℃Melting Point: 50 ~ 53 ℃

NMR, δ(60MHz, CDCl₃/TMS) : 0.65∼2.6(m, singlets at 0.73, 0.90, 0.97, 1.06), 3.10∼3.50(1H, bs), 4.85∼5.15(2H)NMR, δ (60 MHz, CDCl ₃ / TMS): 0.65 to 2.6 (m, singlets at 0.73, 0.90, 0.97, 1.06), 3.10 to 3.50 (1H, bs), 4.85 to 5.15 (2H)

IR(KBr-pellet) νmax(cm^-1) : 3425(m), 2925(s), 2830(s), 1470(m), 1460(m), 1400(w), 1382(m), 1350(w), 1365(m), 1285(w), 1065(w), 1055(w), 1023(m), 1010(w), 980(m), 935(w), 880(w), 820(w), 620(w).IR (KBr-pellet) ν max (cm ^-1 ): 3425 (m), 2925 (s), 2830 (s), 1470 (m), 1460 (m), 1400 (w), 1382 (m), 1350 ( w), 1365 (m), 1285 (w), 1065 (w), 1055 (w), 1023 (m), 1010 (w), 980 (m), 935 (w), 880 (w), 820 ( w), 620 (w).

[실시예 3]Example 3

24-s-에틸-3α,5-시클로-5α-클로스트-22-엔-6-온의 제조Preparation of 24-s-ethyl-3α, 5-cyclo-5α-close-22-en-6-one

i-스티그마스테롤(6.0gr)을 피리딘(80ml)에 녹인다. 여기에 삼산화크롬(6.0gr)을 서서히 더한다. 위의 반응 혼합물을 상온에서 2시간 교반한다. 이때 기벽에 부착되는 물질들을 약수저를 사용 긁어내어 미세한 상태로 만든다. 여기에, 에테르(80ml)을 붓고 잘 교반하면 많은 양의 고온 침전물이 유리됨을 볼 수 있다. 이들을 여과하고, 여과안된 물질을 에테르로 씻은 다음, 모아진 여액에 얼음을 넣어 차게 만든 다음 6N-염산을 넣어서 잘 교반한 후에, 유기층과 수용액층으로 각각 분리한다.Dissolve i-Stigmasterol (6.0 gr) in pyridine (80 ml). Chrome trioxide (6.0 gr) is slowly added thereto. The reaction mixture is stirred at room temperature for 2 hours. At this time, the material attached to the base wall is scraped off using a weak spoon to make a fine state. Pour the ether (80 ml) and stir well to see that a large amount of hot precipitate is liberated. They are filtered, the unfiltered material is washed with ether, and the collected filtrate is iced and iced. Then, the mixture is stirred well with 6N hydrochloric acid, and then separated into an organic layer and an aqueous layer.

수용액층을 2번 더 에테르로 추출한다. 합하여진 에테르층을 얼음을 넣어 차게 만든 후 포화 중탄산나트륨 수용액으로 씻고, 함염수로 씻은 후, 감압하에서 용매를 제거한다. 이렇게 해서 얻어진 물질을 컬럼 크로마토그래피를 한다. 이때 고정상은 실리카겔 60G, 70∼200메쉬이며, 헥산으로 고정상을 채운후, 헥산 : 벤젠 = 1 : 1의 용매 혼합물로 전개시킨다. 이때 85%의 수율로 5.05gr이 얻어졌다.The aqueous layer is extracted twice more with ether. The combined ether layers were cooled with ice, washed with saturated aqueous sodium bicarbonate solution, washed with brine, and then the solvent was removed under reduced pressure. The material thus obtained is subjected to column chromatography. At this time, the stationary phase is silica gel 60G, 70 to 200 mesh, and after filling the stationary phase with hexane, it is developed with a solvent mixture of hexane: benzene = 1: 1. At this time, 5.05 gr was obtained with a yield of 85%.

이를 99% 에탄올에서 재결정하니 흰색의 결정이 얻어졌다.It was recrystallized in 99% ethanol to obtain white crystals.

융점 : 100.5∼101.5℃Melting Point: 100.5 ~ 101.5 ℃

NMR δ(60MHz, CDCl₃/TMS) : 0.73, 0.80, 0.86, 0.90, 1.02, 1.10(18H, CH₃), 1.1∼2.7(26H, CH₂, CH), 5.0∼5.5(2H, m)NMR δ (60 MHz, CDCl ₃ / TMS): 0.73, 0.80, 0.86, 0.90, 1.02, 1.10 (18H, CH ₃ ), 1.1 to 2.7 (26H, CH ₂ , CH), 5.0 to 5.5 (2H, m)

IR ν

(cm^-1) : 2900(s), 2830(s), 1680(s), 1460(s), 1415(w), 1320(w), 1310(m), 1300(s), 1700(w), 1160(w), 1130(w), 1120(w), 1110(w), 1080(w), 1065(w), 1050(w), 1030(w), 1010(w), 980(s), 950(w) , 910(w), 880(w), 820(w), 640(w).IR ν

(cm ^-1 ): 2900 (s), 2830 (s), 1680 (s), 1460 (s), 1415 (w), 1320 (w), 1310 (m), 1300 (s), 1700 (w) , 1160 (w), 1130 (w), 1120 (w), 1110 (w), 1080 (w), 1065 (w), 1050 (w), 1030 (w), 1010 (w), 980 (s) , 950 (w), 910 (w), 880 (w), 820 (w), 640 (w).

[실시예 4]Example 4

24-s-에틸-5α-콜레스타-2,22-디엔-6-온의 제조Preparation of 24-s-ethyl-5α-cholesta-2,22-diene-6-one

24s-에틸-3α,5-시클로-5α-콜레스트-22-엔-6-온(12gr)을 술포란(86ml)에 녹인 용액에, p-톨루엔술폰산(617mg)을 가한다.To a solution of 24s-ethyl-3α, 5-cyclo-5α-cholest-22-en-6-one (12gr) in sulfolane (86 ml), p-toluenesulfonic acid (617 mg) is added.

위의 반응혼합물 상부의 공기를 질소로 충진한 후에 서서히 질소를 불어 넣어 주면서, 160℃ 부근에서 약 90분간을 교반하여 준다. 이때, 반응액의 색깔이 약한 적색을 띄우게 된다. 반응 혼합물을 방치하여 냉각시켜 70∼80℃ 정도까지 내려왔을때, 약 80ml의 물을 서서히 가한다.After filling the air above the reaction mixture with nitrogen, the nitrogen is slowly blown and stirred for about 90 minutes at around 160 ° C. At this time, the color of the reaction solution is light red. When the reaction mixture was left to cool down to about 70-80 ° C., about 80 ml of water was slowly added.

이때 용액에 불용성인 담황색의 고체들이 유리됨을 관찰할 수 있다. 이를 30분간 더 교환한 후에 여과하여, 고체를 취한다. 여액에 대해선, 물(80ml)을 더 첨가한 후에 벤젠과 톨루엔을 1 : 1로 혼합한 용매로 추출한 후에 분리된 유기층을 물로 씻은 후, 분리한 고체와 합한다.At this time, it can be observed that light yellow solids insoluble in the solution are released. It is further exchanged for 30 minutes and then filtered to take a solid. For the filtrate, water (80 ml) is further added, followed by extraction with a solvent in which benzene and toluene are mixed 1: 1, and then the separated organic layer is washed with water and then combined with the separated solid.

이렇게 해서 얻어진 유기층을 감압하에서 용매를 제거한 후, 헥산에 녹인다. 헥산에 불용성인 성분은 술포란이므로 이를 스포이드를 이용 분리해 낸다. 헥산층을 감압하에서 농축한 후 컬럼 크로마토그래피를 이용 물질을 분리해 내었다.(실리카겔 60g, 70∼200메쉬, 헥산으로 충진, 헥산 : 벤젠=1 : 1로 전개).After removing the solvent under reduced pressure, the organic layer thus obtained is dissolved in hexane. The component insoluble in hexane is sulfolane, so it is separated using a dropper. The hexane layer was concentrated under reduced pressure and the material was separated by column chromatography (60 g of silica gel, 70-200 mesh, filled with hexane, hexane: benzene = 1: 1).

7.9gr이 얻어졌다(수율 66%). 99% 에탄올에서 재결정하였다.7.9 gr was obtained (yield 66%). Recrystallized from 99% ethanol.

융점 112.5∼113.0℃Melting Point 112.5 ~ 113.0 ℃

NMR δ(60MHz, CDCl₃/TMS) : 0.69, 0.78, 0.84, 0.88, 0.96, 1.08(18H, CH^- ₃), 1.1∼2.5(24H, -CH₂-CH-), 5.10(2H, m), 5.60(2H, m).NMR δ (60 MHz, CDCl ₃ / TMS): 0.69, 0.78, 0.84, 0.88, 0.96, 1.08 (18H, CH ^- ₃ ), 1.1 to 2.5 (24H, -CH ₂ -CH-), 5.10 (2H, m) , 5.60 (2H, m).

IR ν

(cm^-1) : 2950(s), 2860(s), 1710(s), 1665(w), 1480(m), 1470(m), 1450(m), 1400(m), 1342(w), 1315(w), 1310(w), 1280(w), 1250(w), 1205(w), 1200(w), 1180(w), 1150(w), 1130(w), 1097(w), 1040(w), 1020(w), 1000(m), 950(w), 840(w), 700(m), 640(w).IR ν

(cm ^-1 ): 2950 (s), 2860 (s), 1710 (s), 1665 (w), 1480 (m), 1470 (m), 1450 (m), 1400 (m), 1342 (w) , 1315 (w), 1310 (w), 1280 (w), 1250 (w), 1205 (w), 1200 (w), 1180 (w), 1150 (w), 1130 (w), 1097 (w) , 1040 (w), 1020 (w), 1000 (m), 950 (w), 840 (w), 700 (m), 640 (w).

[실시예 5]Example 5

2α,3α-디히드록시-24s-에틸-5α-콜레스트-22-E-엔-6-온의 제조Preparation of 2α, 3α-dihydroxy-24s-ethyl-5α-cholest-22-E-en-6-one

24s-에틸-5α-콜레스타-22-디엔-6-온(12gr)을 아세톤(600ml)에 녹인 다음, t-부탄올(200ml)에 녹인 4산화오스뮴(600mg) N-메틸-모르포린옥시즈(12gr)과 물(20ml)을 순서대로 가한다. 위의 반응액 상부의 공기를 질소로 치환한 후에, 10시간 동안 교반한다.24s-ethyl-5α-cholesta-22-diene-6-one (12gr) was dissolved in acetone (600 ml), and then osmium tetraoxide (600 mg) N-methyl-morpholine oxide dissolved in t-butanol (200 ml). (12gr) and water (20ml) are added in order. After replacing the air above the reaction solution with nitrogen, it is stirred for 10 hours.

이때 생성된 산물이 결정으로서 석출됨을 볼 수 있다. 반응 혼합물에 포화 중아황산나트륨 용액을 과량으로 존재하는 4산화오스뮴을 파괴하기 위해 첨가한 후 2시간 동안 교반하다. 침전된 결정들을 여과하여 모으고, 여지상의 물질들을 따뜻한 물로 3회 이상 씻어준다.It can be seen that the produced product is precipitated as crystals. Saturated sodium bisulfite solution is added to the reaction mixture to destroy excess osmium tetraoxide and then stirred for 2 hours. The precipitated crystals are collected by filtration and the remaining material is washed three times or more with warm water.

처음 여과한 후의 여액을 조금씩 30∼40℃ 이하에서 감압 농축 후 물을 첨가한 후에 에틸아세테이트로 추출한 다음, 이를 물과 소금물로 씻은 후 무수 황산마그네슘으로 건조후 감압 증류하니 물질(IX)가 얻어졌다.The filtrate after the first filtration was concentrated under reduced pressure little by little at 30-40 ° C., added with water, extracted with ethyl acetate, washed with water and brine, dried over anhydrous magnesium sulfate, and distilled under reduced pressure to obtain a substance (IX). .

이를 헥산하에서 잘 으깨었더니 미세한 분말로 얻어졌다(12.4gr), 수율 95.5%This was crushed well under hexane to give a fine powder (12.4gr), yield 95.5%.

융점 : 204∼207℃Melting Point: 204 ~ 207 ℃

IR ν

(cm^-1) : 3310(m), 2915(s), 2835(m), 1700(s), 1460(w), 1380(w), 1370(w), 1090(w), 1065(w), 1050(m), 1020(w), 980(m).IR ν

(cm ^-1 ): 3310 (m), 2915 (s), 2835 (m), 1700 (s), 1460 (w), 1380 (w), 1370 (w), 1090 (w), 1065 (w) , 1050 (m), 1020 (w), 980 (m).

[실시예 6]Example 6

2α,3α-이소프로필리덴-디옥시-24s-에틸-5α-콜레스트-22-E-엔-6-온의 제조Preparation of 2α, 3α-isopropylidene-dioxy-24s-ethyl-5α-cholest-22-E-en-6-one

2α,3α-디히드록시-24s-에틸-5α-콜레스트-22-E-엔-6-온(7.0gr)을 디클로로메탄(180ml)에 가한 혼합물에 2,2-디-메톡시프로판(20ml)과 p-톨루엔-술폰산(0.33gr)을 가한 다음, 상온에서 1시간 가량 교반한다. 여기에 탄산칼륨 분말을 더한 후 5분간 교반한 뒤에 포화 중탄산나트륨 수용액으로 씻고, 무수 황산마그네슘으로 건조한 후 감압증류하여 용매를 제거하였다. 수율은 정량적이다. 99% 에탄올에서 재결정하였다.To a mixture of 2α, 3α-dihydroxy-24s-ethyl-5α-cholest-22-E-en-6-one (7.0 gr) in dichloromethane (180 ml), 2,2-di-methoxypropane ( 20 ml) and p-toluene-sulfonic acid (0.33 gr) were added, followed by stirring at room temperature for 1 hour. After adding potassium carbonate powder, the mixture was stirred for 5 minutes, washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to remove the solvent. Yield is quantitative. Recrystallized from 99% ethanol.

융점 : 158∼159℃Melting Point: 158-159 ℃

NMR δ(60MHz, CDCl₃/TMS) : 0.60∼2.6(m, singlets at 0.69, 1.33, 1.49), 3.80∼4.40(2H, m), 4.95∼5.24(2H, m).NMR δ (60 MHz, CDCl ₃ / TMS): 0.60 to 2.6 (m, singlets at 0.69, 1.33, 1.49), 3.80 to 4.40 (2H, m), 4.95 to 5.24 (2H, m).

IR ν

(cm^-1) : 2900(s), 2825(s), 1700(s), 1620(s), 1450(m), 1440(w), 1380(s), 1360(s), 1300(w), 1243(s), 1215(s), 1170(w), 1100(w), 1060(s), 1040(m), 1020(m), 990(w), 975(w), 900(w), 850(w), 800(w), 595(w), 510(w).IR ν

(cm ^-1 ): 2900 (s), 2825 (s), 1700 (s), 1620 (s), 1450 (m), 1440 (w), 1380 (s), 1360 (s), 1300 (w) , 1243 (s), 1215 (s), 1170 (w), 1100 (w), 1060 (s), 1040 (m), 1020 (m), 990 (w), 975 (w), 900 (w) , 850 (w), 800 (w), 595 (w), 510 (w).

[실시예 7]Example 7

6,6-에틸렌디옥시-2α,3α-이소프로필리덴디옥시-24s-에틸-5α-콜레스트-22-엔의 제조Preparation of 6,6-ethylenedioxy-2α, 3α-isopropylidenedioxy-24s-ethyl-5α-cholest-22-ene

p-톨루엔술폰산(0.05gr)을 2α,3α-이소프로필리덴디옥시-24s-에틸-5α-콜레스트-22-엔(3.5gr)을 부타논 에틸렌케탈(60ml)에 녹인 용액에 더한다.p-toluenesulfonic acid (0.05gr) is added to a solution of 2α, 3α-isopropylidenedioxy-24s-ethyl-5α-cholest-22-ene (3.5gr) dissolved in butanone ethylene ketal (60 ml).

이 용액을 7시간 동안 환류시킨 다음, 벤젠(50ml)을 더한 후, 1N-수산화나트륨 수용액으로 씻어준다. 이를 물, 함염수 등으로 씻고 무수 황산마그네슘으로 건조한 후 감압하에서 용매를 제거한다. 물질(XI)이 끈끈한 검상으로 얻어졌다(3.2gr, 84% 수율).The solution was refluxed for 7 hours, and then benzene (50 ml) was added, followed by washing with 1N aqueous sodium hydroxide solution. It is washed with water, brine, and the like, dried over anhydrous magnesium sulfate, and the solvent is removed under reduced pressure. Material (XI) was obtained with sticky gum (3.2gr, 84% yield).

NMR δ(60MHz, CDCl₃/TMS) : 0.60∼2.60(m, singlets at 0.63, 1.80, 1.86, 1.96, 1.04, 1.23, 1.38), 3.65∼4.42(6H, m), 4.90∼5.28(2H, m)NMR δ (60 MHz, CDCl ₃ / TMS): 0.60 to 2.60 (m, singlets at 0.63, 1.80, 1.86, 1.96, 1.04, 1.23, 1.38), 3.65 to 4.42 (6H, m), 4.90 to 5.28 (2H, m )

IR ν

(cm^-1) : 2900(s), 2825(s), 1450(m), 1370(m), 1300(w), 1280(w), 1225(w), 1185(m), 1175(m), 1150(w), 1130(w), 1060(s), 1050(s), 1020(w), 975(m), 915(m), 890(w), 870(w), 820(w), 780(w), 670(w), 650(w), 560(w).IR ν

(cm ^-1 ): 2900 (s), 2825 (s), 1450 (m), 1370 (m), 1300 (w), 1280 (w), 1225 (w), 1185 (m), 1175 (m) , 1150 (w), 1130 (w), 1060 (s), 1050 (s), 1020 (w), 975 (m), 915 (m), 890 (w), 870 (w), 820 (w) , 780 (w), 670 (w), 650 (w), 560 (w).

[실시예 8]Example 8

6,6-에틸렌-2α,3α-이소프로필리덴-디옥시-5α-프레그난-20s-카르복스알데히드(일반식(II) 화합물)의 제조Preparation of 6,6-ethylene-2α, 3α-isopropylidene-dioxy-5α-pregnan-20s-carboxaldehyde (General Formula (II) Compound)

물질(XI)(4.0gr : 6,6-에틸렌디옥시-2α,3α-이소프로필리덴디옥시-24s-에틸-5α-콜레스트-22-E-엔)을 디클로로메탄(500ml)과 메탄올(500ml)의 혼합용매에 녹여논 후, 중탄산나트륨(4gr)을 넣은 후 온도를 -60∼50℃로 낮춘 후 오존을 불어 넣는다. 반응 혼합물의 색깔이 엷은 푸른색을 띠우면, 오존 도입을 즉시 중단하고, 냉수욕을 제거한 후 질소를 불어 넣어 과량으로 녹아 있는 오존을 구축해 낸 다음 황화메틸(15ml)을 넣고 3시간 가량 교반시켜 준다. 이를 감압하에서 용매를 제거한 잔여물을 에테르로 추출하면 검상의 표제화합물 3.0gr이 얻어졌다(88.7% 수율).Substance (XI) (4.0 gr: 6,6-ethylenedioxy-2α, 3α-isopropylidenedioxy-24s-ethyl-5α-cholest-22-E-ene) was diluted with dichloromethane (500 ml) and methanol ( After dissolving in 500 ml) of a mixed solvent, sodium bicarbonate (4gr) was added, the temperature was lowered to -60 to 50 ° C, and then ozone was blown. When the reaction mixture is light blue in color, stop the introduction of ozone immediately, remove the cold water bath, blow nitrogen to build up the dissolved ozone, add methyl sulfide (15 ml) and stir for about 3 hours. The solvent was removed under reduced pressure, and the residue was extracted with ether to give 3.0 gr of the title compound (88.7% yield).

NMR δ(60MHz, CDCl₃/TMS) : 0.6∼2.6(m, singlets at 0.71, 1.83), 3.5∼4.35(6H, m), 9.47(1H, d, J₁=3Hz).NMR δ (60 MHz, CDCl ₃ / TMS): 0.6-2.6 (m, singlets at 0.71, 1.83), 3.5-4.35 (6H, m), 9.47 (1H, d, J ₁ = 3 Hz).

IR ν

(cm^-1) : 2670(w), 1715(s), 1460(s), 1450(m), 1370(s), 1340(m), 1305(m), 1285(m), 1230(m), 1190(s), 1175(s), 1150(w), 1130(w), 1060(s), 1050(s), 980(m), 950(w), 920(w), 890(w), 870(w), 820(w), 780(w), 670(w), 640(w), 580(w), 560(w).IR ν

(cm ^-1 ): 2670 (w), 1715 (s), 1460 (s), 1450 (m), 1370 (s), 1340 (m), 1305 (m), 1285 (m), 1230 (m) , 1190 (s), 1175 (s), 1150 (w), 1130 (w), 1060 (s), 1050 (s), 980 (m), 950 (w), 920 (w), 890 (w) , 870 (w), 820 (w), 780 (w), 670 (w), 640 (w), 580 (w), 560 (w).

[실시예 9]Example 9

2α,3α-디히드록시-20{(2-페닐)에테닐}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20 {(2-phenyl) ethenyl} -5α-pregnan-6-one

일반식(II) 화합물(0.38g)과 벤질트리페닐 포스포늄 클로라이드(0.31gr)의 혼합물에 완전히 건조된 에테르(20ml)을 넣고, 용액 상부의 공기를 완전히 건조된 질소로 치환시킨 후 조금씩의 질소가 들어가도록 하여 양압이 반응기 내부에 걸리게 한다. 여기에 교반을 시키면서 나트륨 에톡사이드 용액(15ml, 0.36g의 금속나트륨을 무수에탄올 100ml에 녹인 용액임)을 적가한다.Into a mixture of a compound of formula (II) (0.38g) and benzyltriphenyl phosphonium chloride (0.31gr), completely dried ether (20 ml) was added, and the air at the top of the solution was replaced with completely dried nitrogen, followed by a slight amount of nitrogen. So that positive pressure is trapped inside the reactor. While stirring, a sodium ethoxide solution (15 ml, a solution of 0.36 g of metallic sodium dissolved in 100 ml of anhydrous ethanol) was added dropwise.

환류를 시키면서 10시간 이상 반응을 시킨 다음 물(10ml)을 가한 후, 에테르로써 추출하고, 이를 감압하에서 용매를 제거한 후에 다시 헥산에 녹인 뒤 헥산 불용성 물질을 여과하여 제거하고 이를 감압하에거 농축하고 잔여물을 컬럼 크로마토그래피로 정제하였다.(실시카겔, 230-400메쉬, 헥산-에틸아세테이트=4 : 1) 수율 : 57.6%After reacting for 10 hours or more under reflux, water (10 ml) was added, followed by extraction with ether, which was removed under reduced pressure, and then dissolved in hexane. The hexane-insoluble substance was filtered off and concentrated under reduced pressure. The water was purified by column chromatography. (Sikka gel, 230-400 mesh, hexane-ethyl acetate = 4: 1) Yield: 57.6%

I.R ν

(cm^-1) : 2955(s), 2880(s), 1610(w), 1500(w), 1485(w), 1470(m), 1450(m), 1380(m), 1335(w), 1300(w), 1290(w), 1260(m), 1230(m), 1220(w), 1190(m), 1165(m), 1140(m), 1115(m), 1080(m), 1055(s), 1040(m), 970(w), 950(m), 905(w), 870(w), 850(w), 825(w), 785(w), 775(w), 730(m), 675(w),IR ν

(cm ^-1 ): 2955 (s), 2880 (s), 1610 (w), 1500 (w), 1485 (w), 1470 (m), 1450 (m), 1380 (m), 1335 (w) , 1300 (w), 1290 (w), 1260 (m), 1230 (m), 1220 (w), 1190 (m), 1165 (m), 1140 (m), 1115 (m), 1080 (m) , 1055 (s), 1040 (m), 970 (w), 950 (m), 905 (w), 870 (w), 850 (w), 825 (w), 785 (w), 775 (w) , 730 (m), 675 (w),

NMR (60MHz, CDCl₃/TMS) δ 0.55∼2.45(m, singlets at 0.73, 0.77, 1.05, 1.17, 1.29), 3.60∼4.30(6H, m), 5.65-6.45(2H, m), 7.14(5H, s)NMR (60 MHz, CDCl ₃ / TMS) δ 0.55 to 2.45 (m, singlets at 0.73, 0.77, 1.05, 1.17, 1.29), 3.60 to 4.30 (6H, m), 5.65-6.45 (2H, m), 7.14 (5H , s)

이를 테트라히드로 푸란에 녹여 6N 염산(5ml)을 가하여 밤새 반응시킨 후에, 모든 휘발성(10ml) 성분을 제거한 후, 컬럼 크로마토그래피를 하여 새로운 유사체인 표제 화합물 20을 얻었다. 수율 : 85.6gThis was dissolved in tetrahydrofuran and reacted with 6N hydrochloric acid (5 ml) overnight. After removing all volatile components (10 ml), column chromatography was carried out to obtain the title compound 20 as a new analogue. Yield: 85.6 g

융점 185∼188℃Melting Point 185 ~ 188 ℃

I.R ν

(cm^-1) : 3480(s), 2950(s), 2880(m), 1725(s), 1660(w), 1610(w), 1500(w), 1455(m), 1430(m), 1415(w), 1380(m), 1330(w), 1310(w), 1280(w), 1265(w), 1245(w), 1225(w), 1200(w), 1160(w), 1145(w), 1100(w), 1088(m), 1040(m), 1030(m), 1008(m), 990(w), 960(m), 925(w), 900(w), 860(w), 820(w), 795(w), 735(m), 670(m), 625(w), 595(w), 540(w).IR ν

(cm ^-1 ): 3480 (s), 2950 (s), 2880 (m), 1725 (s), 1660 (w), 1610 (w), 1500 (w), 1455 (m), 1430 (m) , 1415 (w), 1380 (m), 1330 (w), 1310 (w), 1280 (w), 1265 (w), 1245 (w), 1225 (w), 1200 (w), 1160 (w) , 1145 (w), 1100 (w), 1088 (m), 1040 (m), 1030 (m), 1008 (m), 990 (w), 960 (m), 925 (w), 900 (w) , 860 (w), 820 (w), 795 (w), 735 (m), 670 (m), 625 (w), 595 (w), 540 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ : 0.60∼2.45(m, singlets at 0.73, 0.75, 1.07, 1.14, 1.50, 1.65, 1.83, 1.95), 2.50∼2.80(1H, m), 3.55∼4.15(2H, m), 5.80 -6.42(2H, m), 7.23(5H, s).NMR (H, 80 MHz, CDCl ₃ / TMS), δ: 0.60 to 2.45 (m, singlets at 0.73, 0.75, 1.07, 1.14, 1.50, 1.65, 1.83, 1.95), 2.50 to 2.80 (1H, m), 3.55 to 4.15 (2H, m), 5.80 -6.42 (2H, m), 7.23 (5H, s).

[실시예 10]Example 10

2α,3α,6α-트리히드록시-20-{(2-페닐)에테닐}-5α-프레그난-6-온의 제조Preparation of 2α, 3α, 6α-trihydroxy-20-{(2-phenyl) ethenyl} -5α-pregnan-6-one

실시예 9에서 제조된 2α,3α-디히드록시-20-{(2-페닐)에테닐}-5α-프레그난)-6-온(0.2g) 건조THF(10ml)에 녹인 후에 여기에 보란-메틸술피드 컴플렉스(2ml, 10n 용액)을 가하고 상온에서 1시간 동안 교반한다. 그런 다음 3N 수산화나트륨 수용액(2ml)을 점적가한 후, 35%의 과산화 수소용액(2ml)을 가하고 약 1시간 동안 상온에서 교반한 후 감압하에서 증발 건고한다. 건고물을 헥산-에테르에 넣고 충분히 연마하여 결정상의 고체를 얻었다(0.20g).Borane was dissolved in 2α, 3α-dihydroxy-20-{(2-phenyl) ethenyl} -5α-pregnan) -6-one (0.2 g) dried THF (10 ml) prepared in Example 9. Add methylsulfide complex (2 ml, 10n solution) and stir at room temperature for 1 hour. Then, 3N sodium hydroxide aqueous solution (2ml) was added dropwise, 35% hydrogen peroxide solution (2ml) was added thereto, stirred at room temperature for about 1 hour, and evaporated to dryness under reduced pressure. The dried material was poured into hexane-ether and sufficiently ground to give a crystalline solid (0.20 g).

융점 : 204-209℃Melting Point: 204-209 ℃

IR ν

(cm^-1) : 3470(s), 2950(s), 2870(s), 1660(w), 1610(w), 1500(w), 1455(m), 1430(w), 1415(w), 1380(m), 1325(w), 1300(w), 1280(w), 1260(w), 1245(w), 1220(w), 1200(w), 1160(w), 1145(w), 1100(w), 1080(m), 1040(m), 1030(m), 1005(m), 990(w), 960(m), 925(w), 900(w), 860(w), 800(w), 795(w), 735(m), 670(m), 625(w), 595(w), 540(w).IR ν

(cm ^-1 ): 3470 (s), 2950 (s), 2870 (s), 1660 (w), 1610 (w), 1500 (w), 1455 (m), 1430 (w), 1415 (w) , 1380 (m), 1325 (w), 1300 (w), 1280 (w), 1260 (w), 1245 (w), 1220 (w), 1200 (w), 1160 (w), 1145 (w) , 1100 (w), 1080 (m), 1040 (m), 1030 (m), 1005 (m), 990 (w), 960 (m), 925 (w), 900 (w), 860 (w) , 800 (w), 795 (w), 735 (m), 670 (m), 625 (w), 595 (w), 540 (w).

NMR (H, 80MHz, CDCl₃/TMS) δ : 0.60∼2.45(m, singlets at 0.65, 0.74, 1.05, 1.15), 3.55∼4.15(3H, m), 5.80-6.42(2H, m), 7.23(5H, s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ: 0.60 to 2.45 (m, singlets at 0.65, 0.74, 1.05, 1.15), 3.55 to 4.15 (3H, m), 5.80-6.42 (2H, m), 7.23 ( 5H, s).

원소분석(C₂₉H₄₂O₃)Elemental Analysis (C ₂₉ H ₄₂ O ₃ )

계산치(%) : C; 79.47, H; 9.58, O; 10.95Calculated (%): C; 79.47, H; 9.58, 0; 10.95

실측치(%) : C; 78.23, H; 9.92, O; 10.27Found (%): C; 78.23, H; 9.92, O; 10.27

[실시예 11]Example 11

2α,3α-디히드록시-20-{(2-(1-메틸페닐)}에테닐-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(2- (1-methylphenyl)} ethenyl-5α-pregnan-6-one

실시예 9에서 제조된 알데히드(0.38g)와 1-메틸벤질트리페닐 포스포늄 클로라이드로부터 표제 화합물을 제조하였다.The title compound was prepared from aldehyde (0.38 g) and 1-methylbenzyltriphenyl phosphonium chloride prepared in Example 9.

융점 : 194-197℃Melting Point: 194-197 ℃

IR ν

(cm^-1) : 3450(s), 2950(s), 2580(s), 1720(s), 1660(w), 1610(w), 1500(w), 1450(m), 1430(w), 1410(w), 1380(m), 1330(w), 1310(w), 1280(w), 1260(w), 1240(w), 1225(w), 1200(w), 1160(w), 1140(w), 1100(w), 1080(m), 1040(m), 1025(m), 1000(m), 990(w), 950(m), 900(w), 860(w), 820(w), 790(w), 740(m), 645(m).IR ν

(cm ^-1 ): 3450 (s), 2950 (s), 2580 (s), 1720 (s), 1660 (w), 1610 (w), 1500 (w), 1450 (m), 1430 (w) , 1410 (w), 1380 (m), 1330 (w), 1310 (w), 1280 (w), 1260 (w), 1240 (w), 1225 (w), 1200 (w), 1160 (w) , 1140 (w), 1100 (w), 1080 (m), 1040 (m), 1025 (m), 1000 (m), 990 (w), 950 (m), 900 (w), 860 (w) , 820 (w), 790 (w), 740 (m), 645 (m).

NMR (H, 80MHz, CDCl₃/TMS) δ : 0.55∼2.25(m, singlets at 0.73, 0.76, 1.14), 2.30(3H, s), 2.49∼2.80(1H, m), 3.50-4.20(2H, m), 5.80-6.40(2H, m), 7.20(5H, s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ: 0.55 to 2.25 (m, singlets at 0.73, 0.76, 1.14), 2.30 (3H, s), 2.49 to 2.80 (1H, m), 3.50-4.20 (2H, m), 5.80-6.40 (2H, m), 7.20 (5H, s).

원소분석(C₃₀H₄₂O₃)Elemental Analysis (C ₃₀ H ₄₂ O ₃ )

계산치(%) : C; 80.02, H; 9.33, O; 10.65Calculated (%): C; 80.02, H; 9.33, 0; 10.65

실측치(%) : C; 79.52, H; 9.57, O; 10.27Found (%): C; 79.52, H; 9.57, O; 10.27

[실시예 12]Example 12

2α,3α,6α-트리히드록시-20-{2-(1-메틸페닐)}에테닐-5α-프레그난의 제조Preparation of 2α, 3α, 6α-trihydroxy-20- {2- (1-methylphenyl)} ethenyl-5α-pregnan

실시예 11에서 제조된 2α,3α-디히드록시-20-2-(1-메틸페닐)에테닐-5α-프레그난-6-온으로부터, 실시예 10과 동일한 방법으로 제조하였다.From 2α, 3α-dihydroxy-20-2- (1-methylphenyl) ethenyl-5α-pregnan-6-one prepared in Example 11, it was prepared in the same manner as in Example 10.

융점 : 218-221℃Melting Point: 218-221 ℃

IR ν

(cm^-1) : 3460(s), 2950(s), 2860(s), 1660(w), 1615(w), 1500(w), 1450(m), 1430(w), 1410(w), 1380(m), 1335(w), 1310(w), 1280(w), 1260(w), 1240(w), 1220(m), 1160(w), 1140(w), 1105(w), 1080(m), 1050(m), 1030(m), 1000(m), 995(w), 955(m), 900(w), 860(w), 820(w), 785(w), 640(m).IR ν

(cm ^-1 ): 3460 (s), 2950 (s), 2860 (s), 1660 (w), 1615 (w), 1500 (w), 1450 (m), 1430 (w), 1410 (w) , 1380 (m), 1335 (w), 1310 (w), 1280 (w), 1260 (w), 1240 (w), 1220 (m), 1160 (w), 1140 (w), 1105 (w) , 1080 (m), 1050 (m), 1030 (m), 1000 (m), 995 (w), 955 (m), 900 (w), 860 (w), 820 (w), 785 (w) , 640 (m).

NMR (H, 80MHz, CDCl₃/TMS) δ(ppm) : 0.60∼2.40(m, singlets at 0.65, 0.73), 2030(3H, s), 3.50-4.20(3H, m), 5.80-6.42(2H, m), 7.22(5H, s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.60 to 2.40 (m, singlets at 0.65, 0.73), 2030 (3H, s), 3.50-4.20 (3H, m), 5.80-6.42 (2H m), 7.22 (5 H, s).

원소분석(C₃₀H₄₄O₃)Elemental Analysis (C ₃₀ H ₄₄ O ₃ )

계산치(%) : C; 79.66, H; 9.73, O; 10.61Calculated (%): C; 79.66, H; 9.73, 0; 10.61

실측치(%) : C; 78.82, H; 9.26, O; 10.12Found (%): C; 78.82, H; 9.26, O; 10.12

[실시예 13]Example 13

2α,3α-디히드록시-20-{(2-(3-메틸페닐)}에테닐-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(2- (3-methylphenyl)} ethenyl-5α-pregnan-6-one

일반식(II) 화합물(0.38g)과 3-메틸벤질트리페닐 포스포늄 클로라이드(0.32g)에서부터 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 from compound (II) (0.38 g) and 3-methylbenzyltriphenyl phosphonium chloride (0.32 g).

융점 : 192-196℃Melting Point: 192-196 ℃

IR ν

(cm^-1) : 3450(s), 2960(s), 2870(s), 1720(s), 1660(w), 1605(w), 1500(w), 1445(m), 1435(w), 1415(w), 1380(m), 1335(w), 1315(w), 1285(w), 1260(w), 1240(w), 1220(w), 1200(m), 1150(w), 1140(w), 1100(w), 1050(m), 1035(m), 1020(m), 1000(m), 990(w), 955(m), 905(w), 860(w), 850(w), 795(w).IR ν

(cm ^-1 ): 3450 (s), 2960 (s), 2870 (s), 1720 (s), 1660 (w), 1605 (w), 1500 (w), 1445 (m), 1435 (w) , 1415 (w), 1380 (m), 1335 (w), 1315 (w), 1285 (w), 1260 (w), 1240 (w), 1220 (w), 1200 (m), 1150 (w) , 1140 (w), 1100 (w), 1050 (m), 1035 (m), 1020 (m), 1000 (m), 990 (w), 955 (m), 905 (w), 860 (w) , 850 (w), 795 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.55∼2.25(m, singlets at 0.63, 0.73), 2.30(3H, s), 2.48∼2.80(1H, m), 3.50-4.22(2H, m), 5.80-6.38(2H, m), 7.18(5H, s).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.55 to 2.25 (m, singlets at 0.63, 0.73), 2.30 (3H, s), 2.48 to 2.80 (1H, m), 3.50-4.22 ( 2H, m), 5.80-6.38 (2H, m), 7.18 (5H, s).

원소분석(C₃₀H₄₂O₃)Elemental Analysis (C ₃₀ H ₄₂ O ₃ )

실측치(%) : C; 79.98, H; 9.52, O; 10.97Found (%): C; 79.98, H; 9.52, O; 10.97

[실시예 14]Example 14

2α,3α,6α-트리히드록시-20-{(2-(3-메틸페닐)}에테닐-5α-프레그난의 제조Preparation of 2α, 3α, 6α-trihydroxy-20-{(2- (3-methylphenyl)} ethenyl-5α-pregnan

실시예 13에서 제조된 2α,3α-디히드록시-20-{2-(3-메틸페닐)에테닐}-5α-프레그난-6-온(0.2g)을 사용하며, 실시예 10과 동일한 방법으로 제조하였다.2α, 3α-dihydroxy-20- {2- (3-methylphenyl) ethenyl} -5α-pregnan-6-one (0.2 g) prepared in Example 13 was used, and the same method as in Example 10 was used. It was prepared by.

수율 : 0.17gYield: 0.17 g

융점 : 214-215℃Melting Point: 214-215 ℃

IR ν

(cm^-1) : 3460(s), 2960(s), 2870(s), 1650(w), 1600(w), 1500(w), 1440(m), 1430(w), 1410(w), 1380(m), 1330(w), 1310(w), 1280(w), 1260(w), 1240(w), 1215(w), 1200(m), 1150(w), 1145(w), 1100(w), 1040(m), 1030(m), 1020(m), 1000(m), 990(w), 950(m), 900(w), 860(w), 850(w), 780(w).IR ν

(cm ^-1 ): 3460 (s), 2960 (s), 2870 (s), 1650 (w), 1600 (w), 1500 (w), 1440 (m), 1430 (w), 1410 (w) , 1380 (m), 1330 (w), 1310 (w), 1280 (w), 1260 (w), 1240 (w), 1215 (w), 1200 (m), 1150 (w), 1145 (w) , 1100 (w), 1040 (m), 1030 (m), 1020 (m), 1000 (m), 990 (w), 950 (m), 900 (w), 860 (w), 850 (w) 780 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.55∼2.20(m, singlets at 0.63, 0.73, 0.83, 0.89), 2.30(3H, s), 3.50-4.25(3H, m), 5.80-6.35(2H, m), 7.19(5H, s).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.55 to 2.20 (m, singlets at 0.63, 0.73, 0.83, 0.89), 2.30 (3H, s), 3.50-4.25 (3H, m), 5.80-6.35 (2H, m), 7.19 (5H, s).

원소분석(C₃₀H₄₄O₃)Elemental Analysis (C ₃₀ H ₄₄ O ₃ )

실측치(%) : C; 78.12, H; 9.71, O; 11.23Found (%): C; 78.12, H; 9.71, 0; 11.23

[실시예 15]Example 15

2α,3α-디히드록시-20-{2-(2-피코일)}에테닐-5α-프레그난-6-온의 제법Preparation of 2α, 3α-dihydroxy-20- {2- (2-phycoyl)} ethenyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2-피코일 트리페닐 포스포늄 클로라이드(0.31g)을 사용하여 실시예 9와 동일한 방법으로 제조하였다.Compound (II) was prepared in the same manner as in Example 9, using the compound (0.76 g) and 2-phycoyl triphenyl phosphonium chloride (0.31 g).

융점 : 169-172℃Melting Point: 169-172 ℃

IR ν

(cm^-1) : 3450(s), 2950(s), 2580(s), 1725(s), 1600(w), 1575(w), 1540(w), 1460(m), 1440(w), 1420(w), 1330(m), 1310(w), 1270(w), 1260(m), 1220(w), 1200(w), 1100(w), 1080(s), 1050(m), 1220(w), 1200(w), 1100(w), 1080(s), 1050(m), 1000(w), 980(w), 950(w), 940(w), 870(w), 760(w), 750(m), 680(w), 645(w).IR ν

(cm ^-1 ): 3450 (s), 2950 (s), 2580 (s), 1725 (s), 1600 (w), 1575 (w), 1540 (w), 1460 (m), 1440 (w) , 1420 (w), 1330 (m), 1310 (w), 1270 (w), 1260 (m), 1220 (w), 1200 (w), 1100 (w), 1080 (s), 1050 (m) , 1220 (w), 1200 (w), 1100 (w), 1080 (s), 1050 (m), 1000 (w), 980 (w), 950 (w), 940 (w), 870 (w) , 760 (w), 750 (m), 680 (w), 645 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.60∼2.40(m, singlets at 0.63, 0.75), 2.45∼2.92(1H, m), 3.54-4.15(2H, m), 5.80-6.38(2H, m), 6.80-8.56(4H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.60 to 2.40 (m, singlets at 0.63, 0.75), 2.45 to 2.92 (1H, m), 3.54-4.15 (2H, m), 5.80- 6.38 (2H, m), 6.80-8.56 (4H, m).

원소분석(C₂₈H₃₉O₃N)Elemental Analysis (C ₂₈ H ₃₉ O ₃ N)

계산치(%) : C; 76.91, H; 8.92, O; 10.97Calculated (%): C; 76.91, H; 8.92, O; 10.97

실측치(%) : C; 77.84, H; 9.16, O; 11.23Found (%): C; 77.84, H; 9.16, O; 11.23

[실시예 16]Example 16

2α,3α,6α-트리히드록시-20-{2-(2-피코일)}에테닐-5α-프레그난의 제조Preparation of 2α, 3α, 6α-trihydroxy-20- {2- (2-phycoyl)} ethenyl-5α-pregnan

실시예 15에서 제조한 2α,3α-디히드록시-20-{2-(2-피코일)에테닐}-5α-프레그난-6-온(0.2g)에서부터, 실시예 10과 동일한 방법으로 제조하였다.From 2α, 3α-dihydroxy-20- {2- (2-phycoyl) ethenyl} -5α-pregnan-6-one (0.2 g) prepared in Example 15, in the same manner as in Example 10 Prepared.

수율 : 0.18gYield: 0.18 g

융점 : 187-189℃Melting Point: 187-189 ℃

IR ν

(cm^-1) : 3450(s), 2955(s), 2850(s), 1620(w), 1600(w), 1575(w), 1545(m), 1470(m), 1450(m), 1420(m), 1330(w), 1320(w), 1280(m), 1260(m), 1230(w), 1200(w), 1100(w), 1090(s), 1050(m), 1000(w), 980(w), 950(w), 940(w), 880(w), 760(w), 740(m), 695(w), 650(w).IR ν

(cm ^-1 ): 3450 (s), 2955 (s), 2850 (s), 1620 (w), 1600 (w), 1575 (w), 1545 (m), 1470 (m), 1450 (m) , 1420 (m), 1330 (w), 1320 (w), 1280 (m), 1260 (m), 1230 (w), 1200 (w), 1100 (w), 1090 (s), 1050 (m) , 1000 (w), 980 (w), 950 (w), 940 (w), 880 (w), 760 (w), 740 (m), 695 (w), 650 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.60∼2.42(m, singlets at 0.63, 0.75, 0.87), 3.50-4.20(3H, m), 5.81-6.40(2H, m), 6.80-8.55(4H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.60 to 2.42 (m, singlets at 0.63, 0.75, 0.87), 3.50-4.20 (3H, m), 5.81-6.40 (2H, m), 6.80-8.55 (4H, m).

원소분석(C₂₈H₄₁O₃N)Elemental Analysis (C ₂₈ H ₄₁ O ₃ N)

계산치(%) : C; 76.56, H; 9.33, O; 10.92Calculated (%): C; 76.56, H; 9.33, 0; 10.92

실측치(%) : C; 77.48, H; 8.83, O; 11.25Found (%): C; 77.48, H; 8.83, 0; 11.25

[실시예 17]Example 17

2α,3α-디히드록시-20-[2-{(5-메틸)-2-피코일}]에테닐-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- [2-{(5-methyl) -2-picoyl}] ethenyl-5α-pregnan-6-one

일반식(II) 화합물(0.38g)과 (5-메틸)-2-피코일 트리페닐 포스포늄 클로라이드를 사용하여 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 using compound of formula (II) (0.38 g) and (5-methyl) -2-picoyl triphenyl phosphonium chloride.

융점 : 192-196℃Melting Point: 192-196 ℃

IR ν

(cm^-1) : 3450(s), 2950(s), 2850(s), 1720(s), 1600(w), 1570(m), 1540(m), 1500(w), 1460(m), 1455(m), 1430(m), 1380(m), 1330(w), 1310(w), 1280(m), 1260(m), 1230(w), 1210(w), 1100(w), 1080(w), 1045(m), 1005(w), 990(m), 950(w), 940(w), 880(w), 760(w), 745(m), 670(m), 625(w), 580(w).IR ν

(cm ^-1 ): 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1600 (w), 1570 (m), 1540 (m), 1500 (w), 1460 (m) , 1455 (m), 1430 (m), 1380 (m), 1330 (w), 1310 (w), 1280 (m), 1260 (m), 1230 (w), 1210 (w), 1100 (w) , 1080 (w), 1045 (m), 1005 (w), 990 (m), 950 (w), 940 (w), 880 (w), 760 (w), 745 (m), 670 (m) 625 (w), 580 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.55∼2.40(m, singlets at 0.63, 0.75, 0.84, 0.94), 2.40∼3.05(4H, m), 3.55-4.12(2H, m), 5.75-6.42(2H, m), 6.80-8.55(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.55 to 2.40 (m, singlets at 0.63, 0.75, 0.84, 0.94), 2.40 to 3.05 (4H, m), 3.55-4.12 (2H, m ), 5.75-6.42 (2H, m), 6.80-8.55 (3H, m).

원소분석(C₂₉H₄₁O₃N)Elemental Analysis (C ₂₉ H ₄₁ O ₃ N)

계산치(%) : C; 77.18, H; 9.09, O; 10.63Calculated (%): C; 77.18, H; 9.09, O; 10.63

실측치(%) : C; 76.58, H; 8.72, O; 10.52Found (%): C; 76.58, H; 8.72, 0; 10.52

[실시예 18]Example 18

2α,3α,6α-트리히드록시-20-[2-{(5메틸)-2-피코일)}에테닐-5α-프레그난의 제조Preparation of 2α, 3α, 6α-trihydroxy-20- [2-{(5methyl) -2-picoyl)} ethenyl-5α-pregnan

실시예 17에서 제조된 2α,3α-디히드록시-20-[2-{(5-메틸)-2-피코일}]에테닐-5α-프레그난-6-온(0.2g)을 사용하여 실시예 10과 동일한 방법으로 제조하였다.Using 2α, 3α-dihydroxy-20- [2-{(5-methyl) -2-picoyl}] ethenyl-5α-pregnan-6-one (0.2 g) prepared in Example 17 It prepared in the same manner as in Example 10.

융점 : 220-225℃Melting Point: 220-225 ℃

IR ν

(cm^-1) : 3450(s), 2950(s), 2850(s), 1600(w), 1570(m), 1540(m), 1495(w), 1460(m), 1460(m), 1430(m), 1380(m), 1325(w), 1315(w), 1280(m), 1245(m), 1230(w), 1215(w), 1100(w), 1080(w), 1050(m), 1000(w), 995(m), 980(w), 950(w), 940(w), 875(w), 760(w), 745(m), 675(m), 625(w), 580(w).IR ν

(cm ^-1 ): 3450 (s), 2950 (s), 2850 (s), 1600 (w), 1570 (m), 1540 (m), 1495 (w), 1460 (m), 1460 (m) , 1430 (m), 1380 (m), 1325 (w), 1315 (w), 1280 (m), 1245 (m), 1230 (w), 1215 (w), 1100 (w), 1080 (w) , 1050 (m), 1000 (w), 995 (m), 980 (w), 950 (w), 940 (w), 875 (w), 760 (w), 745 (m), 675 (m) 625 (w), 580 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.60∼2.42(m, singlets at 0.64, 0.74, 0.83, 0.95), 2.43-3.02(3H, s), 3.55-4.14(3H, m), 5.76-6.39(2H, m), 6.82-8.52(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.60 to 2.42 (m, singlets at 0.64, 0.74, 0.83, 0.95), 2.43-3.02 (3H, s), 3.55-4.14 (3H, m ), 5.76-6.39 (2H, m), 6.82-8.52 (3H, m).

원소분석(C₂₉H₄₃O₃N)Elemental Analysis (C ₂₉ H ₄₃ O ₃ N)

계산치(%) : C; 76.84, H; 9.49, O; 10.58Calculated (%): C; 76.84, H; 9.49, 0; 10.58

실측치(%) : C; 77.14, H; 9.85, O; 10.62Found (%): C; 77.14, H; 9.85, O; 10.62

[실시예 19]Example 19

2α,3α-디히드록시-20-{2-(3-피코일)}에테닐-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {2- (3-phycoyl)} ethenyl-5α-pregnan-6-one

일반식(II) 화합물(0.38g)과 3-피코일 트리페닐 포스포늄 클로라이드를 사용하여 실시예 9와 동일한 방법으로 제조하였다.Compound (II) was prepared in the same manner as in Example 9 using compound (0.38 g) and 3-phycoyl triphenyl phosphonium chloride.

융점 : 184-187℃Melting Point: 184-187 ℃

IR ν

(cm^-1) : 3450(s), 2950(s), 2850(s), 1720(s), 1600(w), 1570(m), 1540(m), 1470(m), 1455(m), 1420(m), 1330(w), 1310(w), 1280(m), 1260(m), 1230(w), 1200(w), 1100(w), 1080(s), 1050(m), 1000(w), 980(w), 950(w), 940(w), 870(w), 750(w), 680(w).IR ν

(cm ^-1 ): 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1600 (w), 1570 (m), 1540 (m), 1470 (m), 1455 (m) , 1420 (m), 1330 (w), 1310 (w), 1280 (m), 1260 (m), 1230 (w), 1200 (w), 1100 (w), 1080 (s), 1050 (m) , 1000 (w), 980 (w), 950 (w), 940 (w), 870 (w), 750 (w), 680 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.60∼2.40(m, singlets at 0.63, 0.74, 0.83, 1.02, 1.08, 1.17, 1.19), 2.45∼3.00(1H, m), 3.50-4.20(2H, m), 5.82-6.35(2H, m), 6.80-8.55(4H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.60 to 2.40 (m, singlets at 0.63, 0.74, 0.83, 1.02, 1.08, 1.17, 1.19), 2.45 to 3.00 (1H, m), 3.50 -4.20 (2H, m), 5.82-6.35 (2H, m), 6.80-8.55 (4H, m).

원소분석(C₂₈H₃₉O₃N)Elemental Analysis (C ₂₈ H ₃₉ O ₃ N)

실측치(%) : C; 77.12, H; 8.97, O; 11.23Found (%): C; 77.12, H; 8.97, 0; 11.23

[실시예 20]Example 20

2α,3α-트리히드록시-20-{2-(3-피코일)}에테닐-5α-프레그난의 제조Preparation of 2α, 3α-trihydroxy-20- {2- (3-phycoyl)} ethenyl-5α-pregnan

실시예 19에서 제조된 2α,3α-디히드록시-20-{2-(3-피코일)}에테닐-5α-프레그난-6-온(0.2g)을 사용하여 실시예 10과 동일한 방법으로 제조하였다.The same method as Example 10 using 2α, 3α-dihydroxy-20- {2- (3-phycoyl)} ethenyl-5α-pregnan-6-one (0.2 g) prepared in Example 19. It was prepared by.

수율 : 0.19gYield: 0.19 g

융점 : 199-204℃Melting Point: 199-204 ℃

IR ν

(cm^-1) : 3480(s), 2950(s), 2860(s), 1600(w), 1570(m), 1540(m), 1470(w), 1450(m), 1420(m), 1330(w), 1300(w), 1280(m), 1260(m), 1205(w), 1100(w), 1080(s), 1050(m), 1000(w), 980(w), 945(w), 940(w), 870(w), 750(w), 680(w).IR ν

(cm ^-1 ): 3480 (s), 2950 (s), 2860 (s), 1600 (w), 1570 (m), 1540 (m), 1470 (w), 1450 (m), 1420 (m) , 1330 (w), 1300 (w), 1280 (m), 1260 (m), 1205 (w), 1100 (w), 1080 (s), 1050 (m), 1000 (w), 980 (w) , 945 (w), 940 (w), 870 (w), 750 (w), 680 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.60∼2.40(m, singlets at 0.63, 0.75, 0.85, 0.87), 3.52-4.24(3H, m), 5.80-6.40(2H, m), 6.80-8.56(4H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.60 to 2.40 (m, singlets at 0.63, 0.75, 0.85, 0.87), 3.52-4.24 (3H, m), 5.80-6.40 (2H, m ), 6.80-8.56 (4H, m).

원소분석(C₂₈H₄₁O₃N)Elemental Analysis (C ₂₈ H ₄₁ O ₃ N)

실측치(%) : C; 77.18, H; 8.92, O; 11.38Found (%): C; 77.18, H; 8.92, O; 11.38

[실시예 21]Example 21

2α,3α-디히드록시-20-[2-{(2-메틸)-3-피코일}]에테닐-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- [2-{(2-methyl) -3-picoyl}] ethenyl-5α-pregnan-6-one

일반식(II) 화합물(0.38g)과 (2-메틸)-3-피코일 트리페닐 포스포늄 클로라이드(0.31g)을 사용하여 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 using compound of formula (II) (0.38 g) and (2-methyl) -3-picoyl triphenyl phosphonium chloride (0.31 g).

융점 : 192-195℃Melting Point: 192-195 ℃

IR ν

(cm^-1) : 3450(s), 2950(s), 2850(s), 1720(s), 1600(w), 1570(m), 1540(m), 1460(m), 1440(m), 1420(m), 1330(w), 1315(w), 1285(m), 1260(m), 1230(w), 1200(w), 1100(w), 1080(s), 1050(m), 1000(w), 980(w), 950(w), 940(w), 850(w), 750(w), 675(w), 640(w).IR ν

(cm ^-1 ): 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1600 (w), 1570 (m), 1540 (m), 1460 (m), 1440 (m) , 1420 (m), 1330 (w), 1315 (w), 1285 (m), 1260 (m), 1230 (w), 1200 (w), 1100 (w), 1080 (s), 1050 (m) , 1000 (w), 980 (w), 950 (w), 940 (w), 850 (w), 750 (w), 675 (w), 640 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.60∼2.35(m, singlets at 0.64, 0.74, 0.82), 2.35∼3.03(4H, m), 3.55-4.12(2H, m), 5.75-6.45(2H, m), 6.80-8.55(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.60 to 2.35 (m, singlets at 0.64, 0.74, 0.82), 2.35 to 3.03 (4H, m), 3.55-4.12 (2H, m), 5.75-6.45 (2H, m), 6.80-8.55 (3H, m).

원소분석(C₂₉H₄₁O₃N)Elemental Analysis (C ₂₉ H ₄₁ O ₃ N)

실측치(%) : C; 78.26, H; 9.16, O; 11.27Found (%): C; 78.26, H; 9.16, O; 11.27

[실시예 22]Example 22

2α,3α,6α-트리히드록시-20-[2-{(2-메틸)-3-피코일}]에테닐-5α-프레그난의 제조Preparation of 2α, 3α, 6α-trihydroxy-20- [2-{(2-methyl) -3-picoyl}] ethenyl-5α-pregnan

실시예 21에서 제조된 2α,3α-디히드록시-20-[2-{(2-메틸)-3-피코일}]에테닐-5α-프레그난-6-온(0.2g)을 사용하여 실시예 10과 동일한 방법으로 제조하였다.Using 2α, 3α-dihydroxy-20- [2-{(2-methyl) -3-picoyl}] ethenyl-5α-pregnan-6-one (0.2 g) prepared in Example 21 It prepared in the same manner as in Example 10.

융점 : 214-217℃Melting Point: 214-217 ℃

IR ν

(cm^-1) : 3450(s), 2950(s), 2850(s), 1600(w), 1570(m), 1560(m), 1540(m), 1460(m), 1430(m), 1340(w), 1310(w), 1280(m), 1260(m), 1230(w), 1200(w), 1100(w), 1080(s), 1050(m), 1000(w), 980(w), 950(w), 940(w), 840(w), 740(w), 670(w), 640(w).IR ν

(cm ^-1 ): 3450 (s), 2950 (s), 2850 (s), 1600 (w), 1570 (m), 1560 (m), 1540 (m), 1460 (m), 1430 (m) , 1340 (w), 1310 (w), 1280 (m), 1260 (m), 1230 (w), 1200 (w), 1100 (w), 1080 (s), 1050 (m), 1000 (w) , 980 (w), 950 (w), 940 (w), 840 (w), 740 (w), 670 (w), 640 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.6∼2.40(m, singlets at 0.64, 0.75), 2.40-3.03(3H, s), 3.5-4.14(3H, m), 5.72-6.43(2H, m), 6.80-8.53(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.6 to 2.40 (m, singlets at 0.64, 0.75), 2.40-3.03 (3H, s), 3.5-4.14 (3H, m), 5.72- 6.43 (2H, m), 6.80-8.53 (3H, m).

원소분석(C₂₉H₄₃O₃N)Elemental Analysis (C ₂₉ H ₄₃ O ₃ N)

실측치(%) : C; 77.81, H; 8.84, O; 11.26Found (%): C; 77.81, H; 8.84, 0; 11.26

[실시예 23]Example 23

2α,3α-디히드록시-20-[2-{(2-메틸)-4-피코일}]에테닐-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- [2-{(2-methyl) -4-picoyl}] ethenyl-5α-pregnan-6-one

일반식(II) 화합물(0.38g)과 (2-메틸)-4-피코일 트리페닐 포스포늄 클로라이드(0.31g)을 사용하여 실시예 9와 동일한 방법으로 제조하였다.Compound (II) was prepared in the same manner as in Example 9 using compound (0.38 g) and (2-methyl) -4-picoyl triphenyl phosphonium chloride (0.31 g).

융점 : 189-193℃Melting Point: 189-193 ℃

IR ν

(cm^-1) : 3480(s), 2960(s), 2870(s), 1725(s), 1600(w), 1570(m), 1540(m), 1460(m), 1420(m), 1340(w), 1310(w), 1280(m), 1260(m), 1230(w), 1200(w), 1100(w), 1080(s), 1050(m), 1000(w), 970(w), 950(w), 940(w), 830(w), 740(w), 670(w).IR ν

(cm ^-1 ): 3480 (s), 2960 (s), 2870 (s), 1725 (s), 1600 (w), 1570 (m), 1540 (m), 1460 (m), 1420 (m) , 1340 (w), 1310 (w), 1280 (m), 1260 (m), 1230 (w), 1200 (w), 1100 (w), 1080 (s), 1050 (m), 1000 (w) , 970 (w), 950 (w), 940 (w), 830 (w), 740 (w), 670 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.55∼2.40(m, singlets at 0.63, 0.74, 1.07, 1.15), 2.40∼3.05(4H, m), 3.55-4.15(2H, m), 5.70-6.45(2H, m), 6.80-8.58(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.55 to 2.40 (m, singlets at 0.63, 0.74, 1.07, 1.15), 2.40 to 3.05 (4H, m), 3.55-4.15 (2H, m ), 5.70-6.45 (2H, m), 6.80-8.58 (3H, m).

원소분석(C₂₉H₄₁O₃N)Elemental Analysis (C ₂₉ H ₄₁ O ₃ N)

실측치(%) : C; 77.67, H; 8.93, O; 10.27Found (%): C; 77.67, H; 8.93, 0; 10.27

[실시예 24]Example 24

2α,3α,6α-트리히드록시-20-[2-{(2-메틸)-4-피코일}]에테닐-5α-프레그난의 제조Preparation of 2α, 3α, 6α-trihydroxy-20- [2-{(2-methyl) -4-picoyl}] ethenyl-5α-pregnan

실시예 23에서 제조된 2α,3α-디히드록시-20-[2-{(2-메틸)-4-피코일}]에테닐-5α-프레그난-6-온(0.2g)을 사용하여 실시예 10과 동일한 방법으로 제조하였다.Using 2α, 3α-dihydroxy-20- [2-{(2-methyl) -4-picoyl}] ethenyl-5α-pregnan-6-one (0.2 g) prepared in Example 23 It prepared in the same manner as in Example 10.

융점 : 214-218℃Melting Point: 214-218 ℃

IR ν

(cm^-1) : 3450(s), 2950(s), 2850(s), 1600(w), 1570(m), 1560(w), 1540(m), 1465(m), 1430(m), 1340(m), 1310(w), 1305(w), 1280(m), 1260(m), 1230(w), 1200(w), 1100(w), 1080(s), 1050(m), 1000(w), 980(w), 950(w), 940(w), 830(w), 740(w), 680(w).IR ν

(cm ^-1 ): 3450 (s), 2950 (s), 2850 (s), 1600 (w), 1570 (m), 1560 (w), 1540 (m), 1465 (m), 1430 (m) , 1340 (m), 1310 (w), 1305 (w), 1280 (m), 1260 (m), 1230 (w), 1200 (w), 1100 (w), 1080 (s), 1050 (m) , 1000 (w), 980 (w), 950 (w), 940 (w), 830 (w), 740 (w), 680 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.55∼2.35(m, singlets at 0.65, 0.74, 0.83, 0.87), 2.35-3.02(3H, s), 3.55-4.12(3H, m), 5.70-6.42(2H, m), 6.80-8.55(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.55 to 2.35 (m, singlets at 0.65, 0.74, 0.83, 0.87), 2.35-3.02 (3H, s), 3.55-4.12 (3H, m ), 5.70-6.42 (2H, m), 6.80-8.55 (3H, m).

원소분석(C₂₄H₃₈O₃N)Elemental Analysis (C ₂₄ H ₃₈ O ₃ N)

계산치(%) : C; 76.84, H; 9.45, O; 10.58Calculated (%): C; 76.84, H; 9.45, 0; 10.58

실측치(%) : C; 77.89, H; 9.21, O; 11.23Found (%): C; 77.89, H; 9.21, O; 11.23

[실시예 25]Example 25

2α,3α-디히드록시-20-{2-메틸}에테닐-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {2-methyl} ethenyl-5α-pregnan-6-one

일반식(II) 화합물(0.38g)과 에틸트리페닐 포스포늄 브로마이드를 사용하여 실시예 9와 동일한 방법으로 제조하였다.Compound (II) was prepared in the same manner as in Example 9 using 0.38 g of ethyltriphenyl phosphonium bromide.

융점 : 204-209℃Melting Point: 204-209 ℃

IR ν

(cm^-1) : 3450(s), 2950(s), 1720(s), 1600(w), 1570(m), 1470(m), 1460(m), 1440(m), 1430(m), 1385(m), 1335(m), 1280(m), 1260(m), 1230(w), 1200(w), 1190(w), 1150(w), 1100(w), 1070(m), 1050(m), 1040(m), 1000(m), 990(m), 920(w), 890(w), 860(w), 740(w), 700(w), 880(w), 650(w), 640(w).IR ν

(cm ^-1 ): 3450 (s), 2950 (s), 1720 (s), 1600 (w), 1570 (m), 1470 (m), 1460 (m), 1440 (m), 1430 (m) , 1385 (m), 1335 (m), 1280 (m), 1260 (m), 1230 (w), 1200 (w), 1190 (w), 1150 (w), 1100 (w), 1070 (m) , 1050 (m), 1040 (m), 1000 (m), 990 (m), 920 (w), 890 (w), 860 (w), 740 (w), 700 (w), 880 (w) 650 (w), 640 (w).

NMR (H, 80MHz, CDCl₃/TMS), δ(ppm) : 0.60∼2.40(m, singlets at 0.67, 0.75, 0.95), 2.53∼2.80(1H, m), 3.58-4.10(2H, m), 4.90-5.20(2H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.60 to 2.40 (m, singlets at 0.67, 0.75, 0.95), 2.53 to 2.80 (1H, m), 3.58-4.10 (2H, m), 4.90-5.20 (2H, m).

원소분석(C₂₄H₃₈O₃N)Elemental Analysis (C ₂₄ H ₃₈ O ₃ N)

계산치(%) : C; 77.03, H; 10.16, O; 12.82Calculated (%): C; 77.03, H; 10.16, O; 12.82

실측치(%) : C; 76.24, H; 9.25, O; 12.76Found (%): C; 76.24, H; 9.25, O; 12.76

[시험방법][Test Methods]

상기 실시예에서 제조한 브라시노라이드 유사체의 생물학적 활성시험은 벼의 유묘의 라미나 조인트의 굴곡 각도를 알아보는 방법을 사용하였다. 이는 극히 낮은 농도에서도 브라시노라이드 유사체의 활성을 검정할 수 있는 극히 효과적인 방법이다. [참조 : K.Wada, S, Marumo, N. Ikekawa, M, Morisaki 및 K. Mori, Plant and Cell Physiology, 22, 323(1981)] 벼(풍산벼, Oriza sativa, L. cv. Pungsan)를 발아시킨 후, 암실에서 8일간 키운 후에 제2절간의 조인트를 2cm길이로 잘라서, 이를 하루 동안 암실에서 증류수에 띄워놓은 다음, 균일한 조인트를 골라 약제(1% 아세톤, 1% 트윈으로 용액화)로 처리한 다음 2일간 암실에서 띄워 놓는다. 이를 꺼내 녹색광하에서 그의 굴곡각도를 측정한다. 생물 실험의 결과를 하기 표 1에 나타냈다.The biological activity test of the brassinolide analogue prepared in the above example was used to determine the bending angle of the lamina joint of rice seedlings. This is an extremely effective way to assay the activity of brassinolide analogs even at extremely low concentrations. [Ref .: K. Wada, S, Marumo, N. Ikekawa, M, Morisaki and K. Mori, Plant and Cell Physiology, 22, 323 (1981)] Rice (Pungsan, Oriza sativa, L. cv. Pungsan) After germination, grow for 8 days in the dark room, cut the joint between the section 2 into 2cm length, float it in distilled water in the dark room for one day, select a uniform joint, and then use the drug (1% acetone, 1% twin solution). Then leave in the dark for 2 days. Take this out and measure its bending angle under green light. The results of the biological experiments are shown in Table 1 below.

[표 1]TABLE 1

주)^*C는 대조구의 굴곡각도를 나타냄.Note) ^* C indicates the bending angle of the control.

본 발명에 따라 제조된 신규 브라시노라이드 유사체는 상기 표에서 나타난 바와 같이 대조구에 비해 강력한 생리활성을 갖고 있음을 나타냈다.The novel brassinolide analogs prepared according to the present invention showed strong bioactivity compared to the control as shown in the table above.

따라서 본원의 목적물은 연중 일조량이 적은 지방에서 획기적으로 농업에 이용할 수 있으며, 온대, 열대 지방에서는 종래보다 2-3모작 경작에 충분한 효과를 나타내며 특히 경제 작물의 영농을 성취할 수 있는 가능성이 있는 효과를 부여한다.Therefore, the object of the present application can be used for agriculture in the region where the amount of sunshine is low throughout the year, and in the temperate and tropical regions, the effect is sufficient for 2-3 crop cultivation than in the past, and it is possible to achieve the agricultural production of economic crops in particular. To give.

Claims

Brassinolide analogs of general formula (I)

Wherein A represents hydroxy or oxygen, R represents hydrogen, a linear aliphatic group of 1 to 10 carbon atoms, a branched aliphatic group of 3 to 10 carbon atoms, a cyclo group, a methylmethylsulfinyl group, or 1 to 3 substituents Represents an aromatic group which may have a lower alkyl group or a lower alkenyl group, and a heterocyclic group which may have 1 to 3 substituents (wherein the substituent is a lower alkyl group or a lower alkenyl group).

The compound of claim 1, wherein the brassino analog is 2α, 3α-dihydroxy-20-{(2-phenyl) ethenyl} -5α-pregnan-6-one, 2α, 3α-dihydroxy-20- { 2- (1-methylphenyl)} ethenyl} -5α-pregnan-6-one, 2α, 3α-dihydroxy-20- {2- (3-methylphenyl)} ethenyl-5α-pregnan-6- On, 2α, 3α-dihydroxy-20- {2- (2-phycoyl)} ethenyl-5α-pregnan-6-one, 2α, 3α-dihydroxy-20-2-{(5- Methyl) -2-picoyl}] ethenyl-5α-pregnan-6-one, 2α, 3α, 6α-trihydroxy-20- {2- (2-phycoyl)} ethenyl-5α-pregnane , 2α, 3α, 6α-trihydroxy-20- [2-{(5-methyl) -2-picoyl}] ethenyl-5α-pregnan, 2α, 3α, 6α-trihydroxy-20- { 2- (3-phycoyl)} ethenyl-5α-pregnan, 2α, 3α, 6α-trihydroxy-20- [2-{(2-methyl) -3-picoyl}] ethenyl-5α- Pregnane, 2α, 3α, 6α-trihydroxy-20- [2- {2-methyl) -4-picoyl}] ethenyl-5α-pregnan.