KR100951001B1 - New multi-substituted tetrahydrofuran derivatives and method for manufacturing the same - Google Patents
New multi-substituted tetrahydrofuran derivatives and method for manufacturing the same Download PDFInfo
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Abstract
본 발명은 생리활성 천연물 및 의약품에서 다양한 구조로 발현되는 새로운 다중 치환된 테트라하이드로퓨란(Tetrahydrofuran) 유도체 및 상기 유도체를 제조하는 입체선택적 합성방법에 관한 것으로, 본 발명에 따르면 간단한 방법에 의하여 생리활성물질의 중요구조인 새로운 다치환 테트라하이드로퓨란 및 그 유도체를 제공할 수 있다. The present invention relates to a novel multi-substituted tetrahydrofuran derivative expressed in various structures in physiologically active natural products and pharmaceuticals, and to a stereoselective synthesis method for preparing the derivative, according to the present invention. It is possible to provide a new polysubstituted tetrahydrofuran and its derivatives, which are important structures of.
다치환 테트라하이드로퓨란 유도체, 입체선택적 합성방법, 생리활성 천연물 Polysubstituted Tetrahydrofuran Derivatives, Stereoselective Synthesis Method, Bioactive Natural Products
Description
본 발명은 생리활성 천연물 및 의약품에서 다양한 구조로 발현되는 새로운 다중 치환된 테트라하이드로퓨란(Tetrahydrofuran) 유도체 및 상기 유도체를 제조하는 입체선택적 합성방법에 관한 것이다. The present invention relates to novel multi-substituted tetrahydrofuran derivatives expressed in various structures in physiologically active natural products and pharmaceuticals, and to stereoselective synthesis methods for preparing the derivatives.
고도의 비대칭탄소를 가지고 있는 헤테로고리화합물(Heterocycles), 특히 산소를 포함하고 있는 고리화합물(Oxacycles)들은 천연물 및 생리활성물질에서 빈번히 나타나는 단위체이며 항암제, 항생제, 농약 등의 다양한 생리활성을 나타내는 화합물에 나타나는 기본적인 골격으로 알려져 있으며 지금까지 약물 또는 생리활성물질의 원료로서 유용한 것으로 알려져 있다. Heterocycles with highly asymmetric carbons, especially oxcycles containing oxygen, are monomers that are frequently found in natural and bioactive substances and are used in compounds that exhibit various physiological activities such as anticancer agents, antibiotics, and pesticides. It is known as a basic skeleton that appears and is known to be useful as a raw material of drugs or bioactive substances.
상기 화합물들은 대부분 고리화합물로부터 제조되고 있다. 따라서 이들을 얼마나 효율적으로 그리고 얼마나 효용성 있는 합성법의 개발은 매우 긴요하다. 최근에 다양한 전이금속 촉매에 대한 수많은 연구들이 진행되고 있지만 경제 및 산업적인 관점에서 적절한 합성법은 많이 개발되지 못하고 있다 (Zeni, G.; Larock, R. C. Chem . Rev. 2006, 106, 4644-4680; Transition Metals for Organic Synthesis Beller, M.; Bolm, C. Eds.; Weinheim, 2004. (c) Trost, B. M.; Toste, D. Chem . Rev. 2001, 101, 2067-2096). Most of these compounds are prepared from cyclic compounds. Therefore, the development of how efficiently and how effective they are is critical. In recent years, a great deal of research has been conducted on various transition metal catalysts, but from the economic and industrial standpoints, no suitable synthesis has been developed (Zeni, G .; Larock, RC Chem . Rev. 2006, 106 , 4644-4680; Transition). Metals for Organic Synthesis Beller, M .; Bolm, C. Eds .; Weinheim, 2004. (c) Trost, BM; Toste, D. Chem . Rev. 2001, 101 , 2067-2096).
그 중 가장 많이 발견되는 것 중 하나인 테트라하이드로퓨란은 많은 생리활성물질을 구성하는 기본 구조로 잘 알려져 있다 (총설, Reviews: Faul, M. M.; Huff, B. E. Chem . Rev. 2000, 100, 2407-2474; Saleem, M.; Kim, H. J.; Ali, M. S.; Lee, Y. S. Nat. Prod . Rep. 2005, 22, 696-716). 예를 들어 다양한 테트라하이드로퓨란이 포함되어 있는 파마마이신(Pamamycins; Friedman, Doron; Besonov, Alex; Tamarkin, Dov; Eini, Meir. U.S. Pat. Appl. Publ. 2006, U.S. Ser. No. 532,618; Hashimoto, M.; Kozone, I.; Kawaide, H.; Abe, H.; Natsume, M. Journal of Antibiotics 2005, 58, 722-730)은 독특한 항생작용으로 차세대 신약개발 연구에 많은 관심을 모으고 있다. 이외에도 수많은 생리활성 천연물 혹은 합성된 테트라하이드로퓨란 유도체들이 알려져 있다. Tetrahydrofuran, one of the most commonly found, is well known for its basic structure that makes up many bioactive substances (Review, Reviews: Faul, MM; Huff, BE Chem . Rev. 2000, 100 , 2407-2474; Saleem, M .; Kim, HJ; Ali, MS; Lee, YS Nat. Prod . Rep . 2005, 22 , 696-716). For example, Pharmamycins (Famamycins; Friedman, Doron; Besonov, Alex; Tamarkin, Dov; Eini, Meir. US Pat. Appl. Publ. 2006, US Ser.No. 532,618; Hashimoto, M .; Kozone, I .; Kawaide, H .; Abe, H .; Natsume, M. Journal of Antibiotics 2005, 58 , 722-730) are attracting much attention to research on the development of next-generation drugs due to their unique antibiotic action. In addition, numerous biologically active natural or synthetic tetrahydrofuran derivatives are known.
이에 따라 다양한 합성방법이 소개되었다 (총설, Reviews: Wolfe, J. P. Eur . J. Org . Chem. 2007, 571-581; Kang, E. J.; Lee, E. Chem . Rev. 2005, 105, 4348-4378; Boivin, T. L. Tetrahedron 1987, 43, 3309-3362). 많은 테트라하이드로퓨란 합성방법은 카본-산소 결합 형성에 초점이 모아지고 있다. 그러나 이러한 방법은 효율적으로 테트라하이드로퓨란 고리를 형성할 수 있지만 다양한 기능기 도입과 입체선택성에서 문제점이 있는 것으로 지적되고 있다. 이에 따라 옥소늄(Oxonium)중간 체를 이용한 탄소-탄소 결합은 이의 문제점을 극복할 수 있을 것 으로 기대되었다. Accordingly, various synthesis methods have been introduced (Review, Reviews: Wolfe, JP Eur . J. Org . Chem . 2007, 571-581; Kang, EJ; Lee, E. Chem . Rev. 2005, 105 , 4348-4378; Boivin, TL Tetrahedron 1987, 43 , 3309-3362). Many methods of tetrahydrofuran synthesis have focused on the formation of carbon-oxygen bonds. However, this method can efficiently form tetrahydrofuran rings, but it is pointed out that there are problems in introducing various functional groups and stereoselectivity. Accordingly, it was expected that carbon-carbon bonds using Oxonium intermediates could overcome this problem.
상기 기대에 부응하기 위하여 다양한 구조의 테트라하이드로퓨란의 합성에 대한 연구가 진행되었지만(Jaques, T.; Marko, I. E.; Prospisil, J. In Multicomponent Reactions Zhu, J.; Bienayme, H. Eds.; Wiley-VCH: Weinheim, 2005 pp. 398-452; Loh, T.-P.; Hu, Q.-Y.; Tan, K.-T.; Cheng, H.-S. Org . Lett. 2001, 3, 2669-2672; Loh, T.-P.; Hu, Q.-Y.; Ma, L.-T. J. Am . Chem . Soc . 2001, 123, 2450-2451; Mohr, P. Tetrahedron Lett. 1993, 34, 6251-6254), 지금까지 합성방법은 1) 구조적으로 복잡한 출발물질 2) 낮은 입체선택성 3) 기능기의 제한성 등으로 응용성과 효용성에서 문제점으로 지적되었다. In order to meet the above expectations, studies on the synthesis of tetrahydrofuran of various structures have been conducted (Jaques, T .; Marko, IE; Prospisil, J. In Multicomponent). Reactions Zhu, J .; Bienayme, H. Eds .; Wiley-VCH: Weinheim, 2005 pp. 398-452; Loh, T.-P .; Hu, Q.-Y .; Tan, K.-T .; Cheng, H.-S. Org . Lett . 2001, 3 , 2669-2672; Loh, T.-P .; Hu, Q.-Y .; Ma, L.-T. J. Am . Chem . Soc . 2001, 123 , 2450-2451; Mohr, P. Tetrahedron Lett . 1993, 34 , 6251-6254), so far, the synthesis method has been pointed out as a problem in the applicability and utility due to 1) structurally complex starting materials 2) low stereoselectivity 3) functional group limitation.
본 발명에서는 복잡하고 응용성이 풍부한 새로운 다치환 테트라- 하이드로퓨란 화합물을 제공하고자 한다. In the present invention, to provide a new complex multi-substituted tetra- hydrofuran compound is rich in application.
또한, 본 발명은 손쉽게 얻을 수 있는 출발물질로부터 전이금속촉매에 의하여 여러 화학변환을 한 용기내에서 순차적으로 진행시킬 수 있는 간결한 입체선택적 합성을 통하여 다양한 기능기의 도입할 수 있는 다치환 테트라-하이드로퓨란 화합물의 제조방법을 제공하고자 한다. In addition, the present invention provides a polysubstituted tetra-hydro which can introduce various functional groups through concise stereoselective synthesis that can sequentially proceed several chemical transformations in one vessel by a transition metal catalyst from an easily obtained starting material. It is intended to provide a method for preparing a furan compound.
상기 과제를 달성하기 위하여, 본 발명은 하기 화학식 1로 표시되는 다치환 테트라-하이드로퓨란 화합물을 제공한다. In order to achieve the above object, the present invention provides a polysubstituted tetra-hydrofuran compound represented by the following formula (1).
[화학식 1] [Formula 1]
여기서, R1 및 R2는 C1 내지 C20의 알킬, C6 내지 C9의 알릴 또는 C6 내지 C9의아르알킬이다. Where R 1 and R 2 is C 1 to C 20 alkyl, C 6 to C 9 allyl or C 6 to C 9 aralkyl.
바람직하게는 상기 R1 은 PhCH2CH2, n-C5H11, Me, Me2CH 및 Ph로 이루어진 군에서 선택될 수 있고, 상기 R2는 PhCH2CH2, Me, ClCH2, 및 Me2CH로 이루어진 군에서 선택될 수 있다. Preferably the R 1 May be selected from the group consisting of PhCH 2 CH 2 , n- C 5 H 11 , Me, Me 2 CH and Ph, wherein R 2 is PhCH 2 CH 2 , Me, ClCH 2, and Me 2 CH may be selected from the group consisting of.
상기 화학식 1로 표시되는 화합물은 하기 화학식 2로 표시되는 화합물을 출발물질로 하여 제조될 수 있다. The compound represented by Chemical Formula 1 may be prepared by using the compound represented by Chemical Formula 2 as a starting material.
[화학식 2] [Formula 2]
여기서, R1은 상기 화학식 1에서 정의된 바와 같다. Here, R 1 is as defined in the formula (1).
상기 화학식 2로 표시되는 화합물은 종래기술을 응용한 반응식 1과 같이 나타낼 수 있다. 즉, 호모프로파질알코올(homopropargyl alcohols)을 종래 방법(본 연구실에서 개발 된 예, Yu, C.-M.; Yoon, S.-K.; Choi, H.-S.; Baek, K. Chem . Commun. 1997, 763-764)에 의하여 합성하고, 이를 크라베방법(예, Calogeropoulou, T. et al. J. Med . Chem. 2005, 48, 5203-5214; Pyo, S.; Skowron III, J. F.; Cha, J. K. Tetrahedron Lett. 1992, 33, 4703-4706)에 의하여 해당되는 알렌알코올화합물로 전환 하였다. 그리고 나서, 얻어진 알렌 알코올을 클로로트라이메틸실 란(Me3SiCl) 과 트라이에틸아민(Et3N) 존재하에서 반응하여 화학식 2의 화합물들을 합성하였다. The compound represented by Chemical Formula 2 may be represented as in Scheme 1 applying the prior art. In other words, homopropargyl alcohols (homopropargyl alcohols) in the conventional method (Yu, C.-M .; Yoon, S.-K .; Choi, H.-S .; Baek, K. Chem .. Commun synthesized by 1997, 763-764), and it Klein chopping methods (such as, Calogeropoulou, T. et al J. Med Chem 2005, 48, 5203-5214;... Pyo, S .; Skowron III, JF; Cha, JK Tetrahedron Lett . 1992, 33 , 4703-4706) was converted to the corresponding allene alcohol compound. Then, the obtained allene alcohol was reacted in the presence of chlorotrimethylsilane (Me 3 SiCl) and triethylamine (Et 3 N) to synthesize the compound of Formula 2.
[반응식 1] Scheme 1
또한, 본 발명은 하기 화학식 3 내지 화학식 5로 표시되는 테트로-하이드로퓨란 유도체를 제공한다. The present invention also provides a tetra-hydrofuran derivative represented by the following formula (3) to (5).
[화학식 3] (3)
[화학식 4] [Formula 4]
[화학식 5] [Chemical Formula 5]
상기 화학식 3 내지 5에서 R1 및 R2는 상기 화학식 1에서 정의된 바와 같다. R 1 in Formulas 3 to 5 And R 2 is as defined in Formula 1 above.
또한, 본 발명은 (a) 반응플라스크에 화학식 2로 표시되는 출발물질을 용매에 혼합하여 용해하는 단계, (b) 하기 화학식 6으로 표시되는 촉매 및 화학식 7로 표시되는 화합물을 반응기에 투입하여 중간체를 형성하는 단계, 및 (c) 하기 화학식 8 및 9로 표시되는 화합물을 반응기에 투입하여 반응을 완성시키는 단계를 포함하는 다치환 테트라- 하이드로퓨란 화합물의 제조방법을 제공한다. In addition, the present invention (a) mixing and dissolving the starting material represented by the formula (2) in the reaction flask in the reaction flask, (b) the catalyst represented by the following formula (6) and the compound represented by the formula (7) in the reactor to the intermediate It provides a method for producing a polysubstituted tetra-hydrofuran compound comprising the step of, and (c) adding the compound represented by the formula (8) and (9) to the reactor to complete the reaction.
[화학식 6] [Formula 6]
[화학식 7] [Formula 7]
[화학식 8] [Formula 8]
여기서, R2는 상기 화학식 1에서 정의된 바와 같다. Here, R 2 is as defined in the formula (1).
[화학식 9] [Formula 9]
상기 출발물질을 용해하는 용매로는, 특별히 한정하는 것은 아니지만 테트라하이드로퓨란인 것이 바람직하다. Although it does not specifically limit as a solvent which melt | dissolves the said starting material, It is preferable that it is tetrahydrofuran.
상기 (b) 단계는 -10 ~ 10 ℃에서 2 ~ 4 시간 동안 반응시키는 것이 바람직하며, 더욱 바람직하게는 -5 ~ 5 ℃에서 2.5 ~ 3.5 시간 동안 반응시킬 수 있다. The step (b) is preferably reacted for 2 to 4 hours at -10 to 10 ℃, more preferably can be reacted for 2.5 to 3.5 hours at -5 to 5 ℃.
이 경우, 상기 화학식 7로 표시되는 화합물의 첨가량은, 특별히 한정하는 것은 아니지만, 화학식 2로 표시되는 화합물에 대하여 0.9 ~ 1.8 당량으로 첨가하는 것이 바람직하다. In this case, the addition amount of the compound represented by the formula (7) is not particularly limited, but is preferably added in 0.9 to 1.8 equivalents relative to the compound represented by the formula (2).
상기 (c) 단계는 -90 ~ -60 ℃에서 3 ~ 5 시간 동안 반응시키는 것이 바람직하며, 더욱 바람직하게는 -85 ~ -70 ℃에서 3.5 ~ 4.5 시간 동안 반응시킬 수 있다. 특히 -78 ℃에서 진행하는 것이 가장 바람직하다. The step (c) is preferably reacted at -90 to -60 ° C for 3 to 5 hours, more preferably at -85 to -70 ° C for 3.5 to 4.5 hours. It is most preferable to proceed especially at -78 degreeC.
이 경우, 상기 화학식 9로 표시되는 화합물의 첨가량은, 특별히 한정하는 것은 아니지만, 화학식 2로 표시되는 화합물에 대하여 1 ~ 2 당량으로 첨가하는 것이 바람직하다. In this case, although the addition amount of the compound represented by the said Formula (9) is not specifically limited, It is preferable to add in 1-2 equivalents with respect to the compound represented by Formula (2).
본 발명에 따르면 간단한 방법에 의하여 생리활성물질의 중요구조인 새로운 다치환 테트라하이드로퓨란 및 그 유도체를 제공할 수 있다. According to the present invention, a new polysubstituted tetrahydrofuran and its derivatives, which are important structures of the bioactive substance, can be provided by a simple method.
또한, 본 발명에 따른 제조방법은 단순 일-용기(one-pot)반응으로 이에 따라 효율성 증대를 도모할 수 있다. In addition, the production method according to the present invention can be a simple one-pot reaction to thereby increase efficiency.
본 발명은 반응식 2와 같이 손쉽게 얻을 수 있는 화학식 2로 표시되는 화합물로부터 입체선택적으로 제조되는 다양성이 있는 기능기가 포함되어 응용성이 기대되는 화학식 1로 표시되는 화합물을 제공한다. The present invention provides a compound represented by the formula (1) is expected to be applicable to include a variety of functional groups prepared stereoselectively from the compound represented by the formula (2) can be easily obtained as in Scheme 2.
[반응식 2] Scheme 2
본 발명에 따른 다치환 테트라하이드로퓨란의 제조방법은 하기 반응식 3으로 요약되어 표현될 수 있다. The method for preparing polysubstituted tetrahydrofuran according to the present invention can be summarized by the following Scheme 3.
[반응식 3] Scheme 3
즉, 무수 N2분위기하에서 반응을 진행시키면서 반응플라스크에 화학식 2로 표시되는 화합물을 반응용기에 넣은 후 용매로써 테트라히드로퓨란(THF)을 가하였다. 그 후 반응용기에 있는 혼합물에 화학식 7로 표시되는 화합물과 화학식 6으로 표시되는 촉매를 첨가한 후 반응을 진행하였다. 그리고, 상기한 방법으로 생성된 중간체를 냉각시킨 후에 화학식 8로 표시되는 화합물을 첨가하였다. 그 다음 테트라히드로퓨란 (THF)에 묽힌 화학식 9로 표시되는 화합물을 케뉼라를 통해서 한방울씩 첨가하고 반응을 진행하였다. 상기 반응의 진행은 NaHCO3 수용액을 넣어 반응을 종결한 후에 Et2O로 추출한 후에 MgSO4로 건조시켰다. 용매를 감압증류한 후에 실리카젤 크로마토드라피로 정제하여 화학식 1로 표시되는 화합물을 얻을 수 있다. That is, while advancing the reaction under anhydrous N 2 atmosphere, the compound represented by Chemical Formula 2 was placed in a reaction flask in a reaction flask, and then tetrahydrofuran (THF) was added as a solvent. After the addition of the compound represented by the formula (7) and the catalyst represented by the formula (6) to the mixture in the reaction vessel and the reaction was carried out. Then, after cooling the intermediate produced by the above method, the compound represented by the formula (8) was added. Then, the compound represented by the formula (9) diluted in tetrahydrofuran (THF) was added dropwise through the cannula and the reaction proceeded. The reaction proceeded by adding NaHCO 3 aqueous solution to terminate the reaction, followed by extraction with Et 2 O and drying with MgSO 4 . After distilling the solvent under reduced pressure, the compound may be purified by silica gel chromatography to obtain a compound represented by Chemical Formula 1.
합성된 화학식 I의 유도체들은 기능기의 화학변환에 의하여 보다 유용한 다른화합물으로 전환시킬 수 있다. 구체적인 예로는 하기 반응식 4와 같다. The synthesized derivatives of formula I can be converted to other compounds which are more useful by chemical conversion of the functional groups. Specific examples are as in Scheme 4 below.
[반응식 4] Scheme 4
예를 들어 화학식 1의 비닐주석(vinyltin group)은 NIS (N-Iodosuccinimide)에 의하여 화학식 3의 아이오도비닐기(iodovinyl)화합물로 변환시킬 수 있었다. 이 화학식 3의 화합물은 팔라듐촉매 카보닐화반응으로 응용성이 풍부한 화학식 4의 에스터(Ester)로 전환될 수 있었다( 유사 예, Martin, L. D.; Stille, J. K. J. Org . Chem. 1982, 47, 3630-3633). 또한 강염기 NaHMDS (Sodium hexamethyldisilazide) 조건에서 화학식 5 로 전환이 가능하다. For example, the vinyl tin group of Formula 1 could be converted into an iodovinyl compound of Formula 3 by N-Iodosuccinimide (NIS). This compound of Formula 3 could be converted into an ester of Formula 4, which is rich in applicability by palladium-catalyzed carbonylation (Similar examples, Martin, LD; Stille, JK J. Org . Chem . 1982, 47 , 3630 -3633). In addition, it can be converted to the formula (5) under the strong base NaHMDS (Sodium hexamethyldisilazide) conditions.
이하, 실시예를 통해서 본 발명을 더욱 상세히 설명하지만, 하기 실시예들은 단지 본 발명의 구체적 예시일 뿐이며, 본 발명의 보호범위가 하기의 실시예에만 한정되는 것은 아니다. Hereinafter, the present invention will be described in more detail with reference to Examples, but the following Examples are merely specific examples of the present invention, and the protection scope of the present invention is not limited to the following Examples.
[실시예 1] Example 1
(2R,3R,5S)-2,5-디펜에틸-3-(1′-트리메틸스테닐)-비닐테트라히드로퓨란((2R,3R,5S)-2,5-Diphenethyl-3-(1′-trimethylstannyl)-vinyltetrahydrofuran)의 제조 (2R, 3R, 5S) -2,5- dependency ethyl-3- (1'-trimethyl stearyl carbonyl) -vinyl tetrahydrofuran ((2 R, 3 R, 5 S) -2,5-Diphenethyl-3- Preparation of (1′-trimethylstannyl) -vinyltetrahydrofuran)
무수 N2분위기에서 반응플라스크에 화학식 2로 표시되는 화합물(단, R1=PhCH2CH2, 1 당량)을 무게를 달아 반응용기에 넣은 후 용매로써 테트라히드로퓨란(THF)을 가하였다. 그 후 반응용기에 있는 혼합물에 헥사메틸다이틴(hexamethylditin, 1.3 당량)과 촉매로서 π-allylPdCl2(0.005 당량)를 첨가한 후 0℃에서 3시간동안 반응하였다. In anhydrous N 2 atmosphere, a compound represented by Chemical Formula 2 (wherein R 1 = PhCH 2 CH 2 , 1 equivalent) was weighed into a reaction vessel, and tetrahydrofuran (THF) was added as a solvent. Hexamethylditin (1.3 equiv) and π-allylPdCl 2 (0.005 equiv) were added to the mixture in the reaction vessel and reacted at 0 ° C. for 3 hours.
그리고 -78℃로 냉각시킨 후에 화학식 8의 알데히드(다만, R2=PhCH2CH2)를 첨가하였다. 그 다음 -78℃에서 테트라히드로퓨란 (THF)에 묽힌 TMSOTf을 케뉼라를 통해서 한방울씩 첨가한 후, 반응물을 -78℃에서 4시간 동안 반응하였다. 이 때에 NaHCO3 수용액을 넣어 반응을 종결한 후에 Et2O로 추출한 후에 MgSO4로 건조시켰다. 용매를 감압증류한 후에 실리카젤 크로마토그라피로 정제하여 하기 화학식으로 표시되는 화합물을 얻었다. And after cooling to -78 ℃ aldehyde of formula 8 (but, R 2 = PhCH 2 CH 2 ) was added. Then, TMSOTf diluted in tetrahydrofuran (THF) at -78 ° C was added dropwise through the cannula, and the reaction was reacted at -78 ° C for 4 hours. At this time, an aqueous NaHCO 3 solution was added to terminate the reaction, followed by extraction with Et 2 O and drying with MgSO 4 . The solvent was distilled under reduced pressure and purified by silica gel chromatography to obtain a compound represented by the following formula.
수율 : 83% Yield: 83%
TLC , Rf = 0.72 (3:1, Hexanes/EtOAc) TLC, Rf = 0.72 (3: 1, Hexanes / EtOAc)
IR(film) : 3026, 2945, 1608, 1042, 766, 694 cm-1 IR (film): 3026, 2945, 1608, 1042, 766, 694 cm -1
1H NMR (300 MHz, CDCl3) : δ 7.13-7.31 (m, 10H), 5.67 (s, 1H), 5.26 (s, 1H), 3.89-3.99 (m, 2H), 3.16-3.25 (m, 1H), 2.55-2.89 (m, 4H), 1.81-2.07 (m, 3H), 1.67 (dt, J = 12.2 Hz, 10.3Hz, 1H), 1.44-1.52 (m, 2H), 0.12 (s. 9H) 1 H NMR (300 MHz, CDCl 3 ): δ 7.13-7.31 (m, 10H), 5.67 (s, 1H), 5.26 (s, 1H), 3.89-3.99 (m, 2H), 3.16-3.25 (m, 1H), 2.55-2.89 (m, 4H), 1.81-2.07 (m, 3H), 1.67 (dt, J = 12.2 Hz, 10.3 Hz, 1H), 1.44-1.52 (m, 2H), 0.12 (s. 9H )
13C NMR (125MHz, CDCl3) δ153.7, 142.9, 142.6, 129.0, 128.9, 128.8, 128.7, 126.2, 126.1, 125.8, 80.2, 78.6, 52.5, 39.2, 36.0, 35.4, 33.2, 33.1, -8.3 13 C NMR (125 MHz, CDCl 3 ) δ 153.7, 142.9, 142.6, 129.0, 128.9, 128.8, 128.7, 126.2, 126.1, 125.8, 80.2, 78.6, 52.5, 39.2, 36.0, 35.4, 33.2, 33.1, -8.3
MS (ESI) m/z (rel intensity) 470 (M+, 5), 455 (100) MS (ESI) m / z (rel intensity) 470 (M + , 5), 455 (100)
[실시예 2] [Example 2]
(2R,3R,5S)-2-메틸-5-펜에틸-3-(1′-트리메틸스테닐)-비닐-테트라히드로퓨란((2R*,3R*,5S*)-2-Methyl-5-phenethyl-3-(1′- trimethylstannyl)vinyltetrahydrofuran)의 제조 (2R, 3R, 5S) -2-Methyl-5-phenethyl-3- (1′-trimethylstenyl) -vinyl-tetrahydrofuran ((2 R *, 3 R *, 5 S * ) -2- Preparation of Methyl-5-phenethyl-3- (1′- trimethylstannyl) vinyltetrahydrofuran)
R1 = PH2CH2CH2, R2 = Me인 것을 제외하고는 실시예1과 동일한 방법으로 하기 화학식으로 표시되는 화합물을 제조하였다. R 1 = PH 2 CH 2 CH 2 , R 2 A compound represented by the following formula was prepared in the same manner as in Example 1 except that = Me.
수율 : 77% Yield: 77%
TLC, Rf 0.69 (3:1, Hexanes/EtOAc) TLC, R f 0.69 (3: 1, Hexanes / EtOAc)
IR (film) 3027, 2971, 1601, 1082, 917, 768, 699 cm-1 IR (film) 3027, 2971, 1601, 1082, 917, 768, 699 cm -1
1H NMR (400 MHz, CDCl3): δ 7.15-7.30 (m, 10H), 5.70 (s, 1H), 5.29 (s, 1H), 4.17 (p, J = 6.5 Hz, 1H), 3.83-3.93 (m, 1H), 3.14-3.23 (m, 1H), 2.62-2.82 (m, 2H), 1.78-2.05 (m, 3H), 1.67 (dt, J = 11.8 Hz, 10.3 Hz, 1H), 0.95 (d, J = 6.5 Hz, 3H), 0.16 (s. 9H) 1 H NMR (400 MHz, CDCl 3 ): δ 7.15-7.30 (m, 10H), 5.70 (s, 1H), 5.29 (s, 1H), 4.17 (p, J = 6.5 Hz, 1H), 3.83-3.93 (m, 1H), 3.14-3.23 (m, 1H), 2.62-2.82 (m, 2H), 1.78-2.05 (m, 3H), 1.67 (dt, J = 11.8 Hz, 10.3 Hz, 1H), 0.95 ( d, J = 6.5 Hz, 3H), 0.16 (s. 9H)
13C NMR (125 MHz, CDCl3): δ 154.2, 142.5, 128.8, 128.7, 126.1, 125.8, 78.5, 76.9, 52.6, 38.8, 35.8, 33.1, 19.3, -8.3 13 C NMR (125 MHz, CDCl 3 ): δ 154.2, 142.5, 128.8, 128.7, 126.1, 125.8, 78.5, 76.9, 52.6, 38.8, 35.8, 33.1, 19.3, -8.3
MS(ESI) m/z (rel intensity) 380 (M+, 10), 365 (100) MS (ESI) m / z (rel intensity) 380 (M + , 10), 365 (100)
[실시예 3] Example 3
(2R,3R,5S)-5-펜틸-2-펜에틸-3-(1′-트리메틸스테닐)-비닐테트라히드로퓨란((2R*,3R*,5S*)-5-Pentyl-2-phenethyl-3-(1′-trimethylstannyl)vinyl- tetrahydrofuran)의 제조 (2R, 3R, 5S) -5- pentyl-2-phenethyl-3- (1'-trimethyl stearyl carbonyl) -vinyl tetrahydrofuran ((2 R *, 3 R *, 5 S *) -5-Pentyl Preparation of -2-phenethyl-3- (1′-trimethylstannyl) vinyl tetrahydrofuran)
R1=n-C5H11, R2= PhCH2CH2)인 것을 제외하고는 실시예1과 동일한 방법으로 하기 화학식으로 표시되는 화합물을 제조하였다. A compound represented by the following formula was prepared in the same manner as in Example 1 except that R 1 = nC 5 H 11 and R 2 = PhCH 2 CH 2 ).
수율 : 75% Yield: 75%
TLC, Rf : 0.74 (3:1, Hexanes/EtOAc) TLC, R f : 0.74 (3: 1, Hexanes / EtOAc)
IR (film) 3026, 2953, 1601, 1108, 919, 769, 669 cm-1 IR (film) 3026, 2953, 1601, 1108, 919, 769, 669 cm -1
1H NMR (400 MHz, CDCl3) δ 7.23-7.28 (m, 2H), 7.13-7.17 (m, 3H), 5.67 (s, 1H), 5.25 (s, 1H), 3.86-3.97 (m, 2H), 3.15-3.24 (m, 1H), 2.77-2.87 (m, 1H), 2.52-2.62 (m, 1H), 1.97-2.05 (m, 1H), 1.26-1.75 (m, 11H), 0.91 (t, J = 6.5 Hz, 3H), 0.12 (s. 9H) 1 H NMR (400 MHz, CDCl 3 ) δ 7.23-7.28 (m, 2H), 7.13-7.17 (m, 3H), 5.67 (s, 1H), 5.25 (s, 1H), 3.86-3.97 (m, 2H ), 3.15-3.24 (m, 1H), 2.77-2.87 (m, 1H), 2.52-2.62 (m, 1H), 1.97-2.05 (m, 1H), 1.26-1.75 (m, 11H), 0.91 (t , J = 6.5 Hz, 3H), 0.12 (s. 9H)
13C NMR (125 MHz, CDCl3) δ 153.9, 143.1, 128.9, 128.7, 126.0, 125.8, 80.1, 79.5, 52.5, 37.4, 36.0, 35.4, 33.0, 32.4, 26.5, 23.1, 14.5, -8.3 13 C NMR (125 MHz, CDCl 3 ) δ 153.9, 143.1, 128.9, 128.7, 126.0, 125.8, 80.1, 79.5, 52.5, 37.4, 36.0, 35.4, 33.0, 32.4, 26.5, 23.1, 14.5, -8.3
MS (ESI) m/z (rel. intensity): 436 (M+, 9), 421 (100) MS (ESI) m / z (rel. Intensity): 436 (M + , 9), 421 (100)
[실시예 4] Example 4
(2R,3R,5S)-2-메틸-5-펜틸-3-(1′-트리메틸스테닐)-비닐-테트라히드로퓨란((2R*,3R*,5S*)-2-Methyl-5-pentyl-3-(1′-trimethylstannyl)-vinyl-tetrahydrofuran)의 제조 (2R, 3R, 5S) -2-Methyl-5-pentyl-3- (1′-trimethylstenyl) -vinyl-tetrahydrofuran ((2 R *, 3 R *, 5 S * ) -2-Methyl Preparation of -5-pentyl-3- (1′-trimethylstannyl) -vinyl-tetrahydrofuran)
R1=n-C5H11, R2=Me인 것을 제외하고는 실시예 1과 동일한 방법으로 하기 화학식으로 표시되는 화합물을 제조하였다. A compound represented by the following formula was prepared in the same manner as in Example 1 except that R 1 = nC 5 H 11 and R 2 = Me.
수율 : 71% Yield: 71%
TLC, Rf 0.62 (3:1, Hexanes/EtOAc) TLC, R f 0.62 (3: 1, Hexanes / EtOAc)
IR (film) 2956, 2925, 1087, 916 cm-1 IR (film) 2956, 2925, 1087, 916 cm -1
1H NMR (400 MHz, CDCl3) δ5.69 (t, J = 2.4 Hz, 1H), 5.29 (t, J = 1.9 Hz, 1H), 4.15 (p, J = 8.4 Hz, 1H), 3.80-3.89 (m, 1H), 3.17 (m, 1H), 2.00 (m, 1H), 1.25-1.72 (m, 9H), 0.92 (d, J = 8.4Hz, 3H), 0.86 (t, J = 9.2 Hz, 3H), 0.16 (s, 9H) 1 H NMR (400 MHz, CDCl 3 ) δ 5.69 (t, J = 2.4 Hz, 1H), 5.29 (t, J = 1.9 Hz, 1H), 4.15 (p, J = 8.4 Hz, 1H), 3.80- 3.89 (m, 1H), 3.17 (m, 1H), 2.00 (m, 1H), 1.25-1.72 (m, 9H), 0.92 (d, J = 8.4 Hz, 3H), 0.86 (t, J = 9.2 Hz , 3H), 0.16 (s, 9H)
13C NMR (125 MHz, CDCl3) δ156.6, 128.0, 81.6, 79.1, 54.8, 39.3, 38.3, 34.7, 28.7, 25.3, 21.5, 16.7, -6.0 13 C NMR (125 MHz, CDCl 3 ) δ 156.6, 128.0, 81.6, 79.1, 54.8, 39.3, 38.3, 34.7, 28.7, 25.3, 21.5, 16.7, -6.0
MS (ESI) m/z (rel. intensity) 346 (M+, 8), 331(100) MS (ESI) m / z (rel. Intensity) 346 (M + , 8), 331 (100)
[실시예 5] Example 5
(2S,3R,5S)-2-(클로로메틸)-5-펜틸-3-(1′-트리메틸스테닐)-비닐테트라히드로퓨란((2S*,3R*,5S*)-2-(Chloromethyl)-5-pentyl-3-(1′-trimethylstannyl)-vinyltetrahydrofuran)의 제조 (2S, 3R, 5S) -2- ( chloromethyl) -5-pentyl-3- (1'-trimethyl stearyl carbonyl) -vinyl tetrahydrofuran ((2 S *, 3 R *, 5 S *) -2 Preparation of-(Chloromethyl) -5-pentyl-3- (1′-trimethylstannyl) -vinyltetrahydrofuran)
R1=n-C5H11, R2=CH2Cl인 것을 제외하고는 실시예 1과 동일한 방법으로 하기 화학식으로 표시되는 화합물을 제조하였다. A compound represented by the following formula was prepared in the same manner as in Example 1 except that R 1 = nC 5 H 11 and R 2 = CH 2 Cl.
수율 : 69% Yield: 69%
TLC, Rf 0.65 (3:1, Hexanes/EtOAc) TLC, R f 0.65 (3: 1, Hexanes / EtOAc)
IR (film) 2957, 2928, 1461, 1110 cm-1 IR (film) 2957, 2928, 1461, 1110 cm -1
1H NMR (400 MHz, CDCl3) δ 5.77 (t, J = 1.9 Hz, 1H), 5.34 (t, J = 1.9 Hz, 1H), 4.16 (m, 1H), 3.95 (m, 1H), 3.21-3.38 (m, 3H), 2.04 (m, 1H), 1.25-1.80 (m, 9H), 0.89 (t, J = 6.8 Hz, 3H), 0.18 (s, 9H) 1 H NMR (400 MHz, CDCl 3 ) δ 5.77 (t, J = 1.9 Hz, 1H), 5.34 (t, J = 1.9 Hz, 1H), 4.16 (m, 1H), 3.95 (m, 1H), 3.21 -3.38 (m, 3H), 2.04 (m, 1H), 1.25-1.80 (m, 9H), 0.89 (t, J = 6.8 Hz, 3H), 0.18 (s, 9H)
13C NMR (125 MHz, CDCl3) δ 152.4, 126.9, 80.7, 79.9, 51.9, 46.8, 36.6, 36.1, 32.3, 26.2, 23.0, 14.5, -8.3 13 C NMR (125 MHz, CDCl 3 ) δ 152.4, 126.9, 80.7, 79.9, 51.9, 46.8, 36.6, 36.1, 32.3, 26.2, 23.0, 14.5, -8.3
MS (ESI) m/z (rel. intensity) 403 (M+Na+, 5), 380 (M+, 60), 365 (30), 345 (11) MS (ESI) m / z (rel. Intensity) 403 (M + Na + , 5), 380 (M + , 60), 365 (30), 345 (11)
[실시예 6] Example 6
(2R,3R,5S)-5-메틸-2-펜에틸-3-(1′-트리메틸스테닐)-비닐테트라히드로퓨란 ((2R*,3R*,5S*)-5-Methyl-2-phenethyl-3-(1′-trimethylstannyl)-viyl-tetrahydrofuran)의 제조 (2R, 3R, 5S) -5-Methyl-2-phenethyl-3- (1′-trimethylstenyl) -vinyltetrahydrofuran ((2 R *, 3 R *, 5 S * ) -5-Methyl Preparation of -2-phenethyl-3- (1′-trimethylstannyl) -viyl-tetrahydrofuran)
R1=Me, R2=PH2CH2CH2인 것을 제외하고는 실시예 1과 동일한 방법으로 하기 화학식으로 표시되는 화합물을 제조하였다. A compound represented by the following formula was prepared in the same manner as in Example 1, except that R 1 = Me, R 2 = PH 2 CH 2 CH 2 .
수율 : 87% Yield: 87%
TLC, Rf 0.69 (3:1, Hexanes/EtOAc) TLC, R f 0.69 (3: 1, Hexanes / EtOAc)
IR (flim) 3024, 2970, 1603, 1089, 909, 763, 695 cm-1 IR (flim) 3024, 2970, 1603, 1089, 909, 763, 695 cm -1
1H NMR (400 MHz, CDCl3) δ7.23-7.28 (m, 2H), 7.13-7.18 (m, 3H), 5.67 (s, 1H), 5.25 (s, 1H), 3.89-4.09 (m, 2H), 3.21 (m, 1H), 2.78-2.87 (m, 1H), 2.53-2.63 (m, 1H), 2.02-2.10 (m, 1H), 1.46-1.65 (m, 3H), 1.33 (d, J = 6.1 Hz, 3H), 0.13 (s, 9H) 1 H NMR (400 MHz, CDCl 3 ) δ7.23-7.28 (m, 2H), 7.13-7.18 (m, 3H), 5.67 (s, 1H), 5.25 (s, 1H), 3.89-4.09 (m, 2H), 3.21 (m, 1H), 2.78-2.87 (m, 1H), 2.53-2.63 (m, 1H), 2.02-2.10 (m, 1H), 1.46-1.65 (m, 3H), 1.33 (d, J = 6.1 Hz, 3H), 0.13 (s, 9H)
13C NMR (125 MHz, CDCl3) δ154.2, 143.0, 128.9, 128.7, 126.0, 125.9, 80.6, 75.2, 52.9, 38.3, 35.4, 33.0, 22.3, -8.2 13 C NMR (125 MHz, CDCl 3 ) δ 154.2, 143.0, 128.9, 128.7, 126.0, 125.9, 80.6, 75.2, 52.9, 38.3, 35.4, 33.0, 22.3, -8.2
MS (ESI) m/z (rel. intensity) 413 (65), 380 (M+, 7), 365 (9), 245 (100) MS (ESI) m / z (rel. Intensity) 413 (65), 380 (M + , 7), 365 (9), 245 (100)
[실시예 7] Example 7
(2R,3R,5R)-5-이소프로필-2-펜에틸-3-(1′-트리메틸스테닐)-비닐테트라히드로퓨란((2R*,3R*,5R*)-5-Isopropyl-2-phenethyl-3-(1′-trimethylstannyl)vinyl-tetrahydrofuran)의 제조 (2R, 3R, 5R) -5- isopropyl-2-phenethyl-3- (1'-trimethyl stearyl carbonyl) -vinyl tetrahydrofuran ((2 R *, 3 R *, 5 R *) -5- Preparation of Isopropyl-2-phenethyl-3- (1′-trimethylstannyl) vinyl-tetrahydrofuran)
단, R1=Me2CH, R2=PH2CH2CH2인 것을 제외하고는 실시예 1과 동일한 방법으로 하기 화학식으로 표시되는 화합물을 제조하였다. However, except that R 1 = Me 2 CH, R 2 = PH 2 CH 2 CH 2 A compound represented by the following formula was prepared in the same manner as in Example 1.
수율 : 76% Yield: 76%
TLC, Rf 0.75 (3:1, Hexanes/EtOAc) TLC, R f 0.75 (3: 1, Hexanes / EtOAc)
IR (film) 3020, 2968, 2872, 11018, 921, 765, 672 cm-1 IR (film) 3020, 2968, 2872, 11018, 921, 765, 672 cm -1
1H NMR (400 MHz, CDCl3) δ 7.23-7.28 (m, 2H), 7.12-7.17 (m, 3H), 5.68 (t, J = 2.4 Hz, 1H), 5.26 (s, 1H), 3.95-4.01 (m, 1H), 3.59-3.66 (m, 1H), 3.18-3.26 (m, 1H), 2.78-2.88 (m, 1H), 2.51-2.59 (dt, J = 18.4 Hz, 11.2 Hz, 1H), 1.88-1.96 (m, 1H), 1.63-1.76 (m, 2H), 1.38-1.45 (m, 2H), 1.05 (d, J = 9.2Hz, 3H), 0.90 (d, J = 9.2Hz, 3H), 0.11(s. 9H) 1 H NMR (400 MHz, CDCl 3 ) δ 7.23-7.28 (m, 2H), 7.12-7.17 (m, 3H), 5.68 (t, J = 2.4 Hz, 1H), 5.26 (s, 1H), 3.95- 4.01 (m, 1H), 3.59-3.66 (m, 1H), 3.18-3.26 (m, 1H), 2.78-2.88 (m, 1H), 2.51-2.59 (dt, J = 18.4 Hz, 11.2 Hz, 1H) , 1.88-1.96 (m, 1H), 1.63-1.76 (m, 2H), 1.38-1.45 (m, 2H), 1.05 (d, J = 9.2 Hz, 3H), 0.90 (d, J = 9.2 Hz, 3H ), 0.11 (s. 9H)
13C NMR (125 MHz, CDCl3) δ 153.3, 143.1, 128.9, 128.7, 126.0, 125.5, 85.1, 79.8, 52.4, 35.5, 34.9, 33.1, 20.2, 19.1, -8.4 13 C NMR (125 MHz, CDCl 3 ) δ 153.3, 143.1, 128.9, 128.7, 126.0, 125.5, 85.1, 79.8, 52.4, 35.5, 34.9, 33.1, 20.2, 19.1, -8.4
MS (ESI) m/z (rel. intensity) 408 (M+, 5), 393 (100), 384 (10) MS (ESI) m / z (rel. Intensity) 408 (M + , 5), 393 (100), 384 (10)
[실시예 8] Example 8
(2R,3R,5R)-2-펜에틸-5-페닐-3-(1′-트리메틸스테닐)-비닐테트라히드로퓨란((2R*,3R*,5R*)-2-Phenethyl-5-phenyl-3-(1′-trimethylstannyl)vinyl-tetrahydrofuran)의 제조 (2R, 3R, 5R) -2- phenethyl-5-phenyl-3- (1'-trimethyl stearyl carbonyl) -vinyl tetrahydrofuran ((2 R *, 3 R *, 5 R *) -2-Phenethyl Preparation of -5-phenyl-3- (1′-trimethylstannyl) vinyl-tetrahydrofuran)
R1=Ph, R2=PH2CH2CH2인 것을 제외하고는 실시예 1과 동일한 방법으로 하기 화학식으로 표시되는 화합물을 제조하였다. A compound represented by the following formula was prepared in the same manner as in Example 1, except that R 1 = Ph, R 2 = PH 2 CH 2 CH 2 .
수율 : 67% Yield: 67%
TLC, Rf 0.73 (3:1, Hexanes/EtOAc) TLC, R f 0.73 (3: 1, Hexanes / EtOAc)
IR (film) 3027, 2923, 1602, 1052, 756, 698 cm-1 IR (film) 3027, 2923, 1602, 1052, 756, 698 cm -1
1H NMR (400 MHz, CDCl3) δ 7.34-7.42 (m, 4H), 7.25-7.30 (m, 3H), 7.15-7.21 (m, 3H), 5.67 (t, J = 1.9 Hz, 1H), 5.28 (t, J = 1.9 Hz, 1H), 5.02 (dd, J = 14.4 Hz, 5.5 Hz, 1H), 4.16-4.24 (m, 1H), 3.38-3.46 (m, 1H), 2.92-3.02 (m, 1H), 2.63-2.73 (m, 1H), 2.26-2.34 (m, 1H), 1.92-2.04 (m, 1H), 1.46-1.68 (m, 2H), 0.12 (s. 9H) 1 H NMR (400 MHz, CDCl 3 ) δ 7.34-7.42 (m, 4H), 7.25-7.30 (m, 3H), 7.15-7.21 (m, 3H), 5.67 (t, J = 1.9 Hz, 1H), 5.28 (t, J = 1.9 Hz, 1H), 5.02 (dd, J = 14.4 Hz, 5.5 Hz, 1H), 4.16-4.24 (m, 1H), 3.38-3.46 (m, 1H), 2.92-3.02 (m , 1H), 2.63-2.73 (m, 1H), 2.26-2.34 (m, 1H), 1.92-2.04 (m, 1H), 1.46-1.68 (m, 2H), 0.12 (s. 9H)
13C NMR (125 MHz, CDCl3) δ 152.7, 143.6, 142.8, 129.0, 128.7, 127.6, 126.1, 125.9, 81.0, 80.4, 52.7, 38.7, 35.7, 33.1, -8.4 13 C NMR (125 MHz, CDCl 3 ) δ 152.7, 143.6, 142.8, 129.0, 128.7, 127.6, 126.1, 125.9, 81.0, 80.4, 52.7, 38.7, 35.7, 33.1, -8.4
MS (ESI) m/z (rel. intensity) 443 (5), 442 (M+, 5), 427 (100), 395 (10) MS (ESI) m / z (rel. Intensity) 443 (5), 442 (M + , 5), 427 (100), 395 (10)
[실시예 9] Example 9
(2R,3R,5R)-2-이소프로필-5-페닐-3-(1′-트리메틸스테닐)-비닐테트라히드로퓨란((2R*,3R*,5R*)-2-Isopropyl-5-phenyl-3-(1′-trimethylstannyl)vinyl-tetrahydrofuran)의 제조 (2R, 3R, 5R) -2- isopropyl-5-phenyl-3- (1'-trimethyl stearyl carbonyl) -vinyl tetrahydrofuran ((2 R *, 3 R *, 5 R *) -2-Isopropyl Preparation of -5-phenyl-3- (1′-trimethylstannyl) vinyl-tetrahydrofuran)
R1=Ph, R2=Me2CH인 것을 제외하고는 실시예 1과 동일한 방법으로 하기 화학식으로 표시되는 화합물을 제조하였다. A compound represented by the following formula was prepared in the same manner as in Example 1 except that R 1 = Ph and R 2 = Me 2 CH.
수율 : 53% Yield: 53%
TLC, Rf 0.73 (3:1, Hexanes/EtOAc) TLC, R f 0.73 (3: 1, Hexanes / EtOAc)
IR (film) 3031, 2958, 2926, 1602, 1086, 750, 700 cm-1 IR (film) 3031, 2958, 2926, 1602, 1086, 750, 700 cm -1
1H NMR (300 MHz, CDCl3) δ 7.34-7.42 (m, 4H), 7.25-7.30 (m, 3H), 7.15-7.21 (m, 3H), 5.67 (t, J = 1.9 Hz, 1H), 5.28 (t, J = 1.9 Hz, 1H), 5.02 (dd, J = 14.4 Hz, 5.5 Hz, 1H), 4.16-4.24 (m, 1H), 3.38-3.46 (m, 1H), 2.92-3.02 (m, 1H), 2.63-2.73 (m, 1H), 2.26-2.34 (m, 1H), 1.92-2.04 (m, 1H), 1.46-1.68 (m, 2H), 0.12 (s. 9H) 1 H NMR (300 MHz, CDCl 3 ) δ 7.34-7.42 (m, 4H), 7.25-7.30 (m, 3H), 7.15-7.21 (m, 3H), 5.67 (t, J = 1.9 Hz, 1H), 5.28 (t, J = 1.9 Hz, 1H), 5.02 (dd, J = 14.4 Hz, 5.5 Hz, 1H), 4.16-4.24 (m, 1H), 3.38-3.46 (m, 1H), 2.92-3.02 (m , 1H), 2.63-2.73 (m, 1H), 2.26-2.34 (m, 1H), 1.92-2.04 (m, 1H), 1.46-1.68 (m, 2H), 0.12 (s. 9H)
13C NMR (75 MHz, CDCl3) δ 155.4, 142.4, 128.3, 127.1, 126.4, 125.8, 87.8, 79.5, 52.3, 41.1, 29.4, 19.9, 19.6, -7.9 13 C NMR (75 MHz, CDCl 3 ) δ 155.4, 142.4, 128.3, 127.1, 126.4, 125.8, 87.8, 79.5, 52.3, 41.1, 29.4, 19.9, 19.6, -7.9
GC/MS (EI) m/z (rel intensity) 380 (M+, 5), 365 (100), 293 (77), 165 (43), 143 (75) GC / MS (EI) m / z (rel intensity) 380 (M + , 5), 365 (100), 293 (77), 165 (43), 143 (75)
[실시예 10] Example # 10
(2R*,3R*,5S*)-3-(1-아이오도비닐)-5-펜틸-2-펜에틸-테트라히드로퓨란((2R*,3R*,5S*)-3-(1-Iodovinyl)-5-pentyl-2-phenethyl-tetrahydrofuran)의 제조 (2 R *, 3 R * , 5 S *) - 3- (1- iodo-vinyl) -5-pentyl-2-phenethyl-tetrahydro-furan ((2 R *, 3 R *, 5 S *) Preparation of -3- (1-Iodovinyl) -5-pentyl-2-phenethyl-tetrahydrofuran)
반응용기에 CH2Cl2에 있는(2R,3R,5S)-5-펜틸-2-펜에틸-3-(1′-트리메틸스테닐)-비닐테트라히드로퓨란(44.8mg, 0.103mmol)을 -78℃에서 첨가하였다. 그리고 N-아이오도쑥씬이미드(N-Iodosuccinimide) (46.3mg, 0.206mmol)을 첨가하였다. (2R, 3R, 5S) -5-pentyl-2-phenethyl-3- (1′-trimethylstenyl) -vinyltetrahydrofuran (44.8 mg, 0.103 mmol) in CH 2 Cl 2 was added to the reaction vessel. Add at 78 ° C. N-Iodosuccinimide (46.3 mg, 0.206 mmol) was added.
그 후 혼합용액을 -78℃에서 2시간 동안 반응시키고 다시 -40℃에서 20분 동안 반응하였다. 그리고 혼합용액을 상온에서 반응시켰다. 이 때에 물을 넣어 반응을 종결한 후에 CH2Cl2로 추출한 후에 Na2S2O3로 건조시켰다. 용매를 감압증류한 후에 실리카젤 크로마토그래피로 정제하여 하기 화학식으로 표시되는 화합물을 얻었다. Thereafter, the mixed solution was reacted at -78 ° C for 2 hours and again at -40 ° C for 20 minutes. And the mixed solution was reacted at room temperature. At this time, water was added to terminate the reaction, followed by extraction with CH 2 Cl 2 and drying with Na 2 S 2 O 3 . The solvent was distilled under reduced pressure and purified by silica gel chromatography to obtain a compound represented by the following formula.
수율 : 93% Yield: 93%
TLC, Rf : 0.55 (15:1, Hexanes/EtOAc) TLC, Rf: 0.55 (15: 1, Hexanes / EtOAc)
IR (film) 3024, 2952, 1065, 770, 693, 665 cm-1 IR (film) 3024, 2952, 1065, 770, 693, 665 cm-1
1H NMR (400 MHz, CDCl3) δ 7.17-7.30 (m, 5H), 6.09 (s, 1H), 5.84 (s, 1H), 3.90-4.04 (m, 2H), 3.18-3.26 (m, 1H), 2.83-2.92 (m, 1H), 2.60-2.71 (m, 1H), 2.04-2.16 (m, 1H), 1.25-1.79 (m, 9H), 0.89 (t, J = 6.9 Hz, 3H) 1 H NMR (400 MHz, CDCl 3 ) δ 7.17-7.30 (m, 5H), 6.09 (s, 1H), 5.84 (s, 1H), 3.90-4.04 (m, 2H), 3.18-3.26 (m, 1H) , 2.83-2.92 (m, 1H), 2.60-2.71 (m, 1H), 2.04-2.16 (m, 1H), 1.25-1.79 (m, 9H), 0.89 (t, J = 6.9 Hz, 3H)
13C NMR (125 MHz, CDCl3) δ 145.0, 131.2, 130.9, 128.8, 128.3, 112.0, 82.6, 81.9, 57.9, 39.4, 39.2, 35.9, 35.2, 34.5, 28.6, 25.3, 16.7 13C NMR (125 MHz, CDCl 3 ) δ 145.0, 131.2, 130.9, 128.8, 128.3, 112.0, 82.6, 81.9, 57.9, 39.4, 39.2, 35.9, 35.2, 34.5, 28.6, 25.3, 16.7
MS (ESI) m/z (rel. intensity) 421 (M+Na+, 20), 399 (72), 398 (M+, 5), 253 (100) MS (ESI) m / z (rel. Intensity) 421 (M + Na + , 20), 399 (72), 398 (M +, 5), 253 (100)
Anal. Calcd for C19H27IO: C, 57.29; H, 6.83; I, 31.86; O, 4.02. Found: C, 57.57 H, 6.61. Anal. Calcd for C 19 H 27 IO: C, 57.29; H, 6.83; I, 31.86; O, 4.02. Found: C, 57.57 H, 6.61.
[실시예 11] Example 11
메틸 2-{(2R*,3S*,5S*)-5-펜틸-2-펜에틸-테트라히드로퓨란-3-일}아크릴레이트(Methyl 2-{(2R*,3S*,5S*)-5-pentyl-2-phenethyl-tetrahydrofuran-3-yl} acrylate)의 제조 Methyl 2 - {(2 R *, 3 S *, 5 S *) - 5- pentyl-2-phenethyl-tetrahydro-furan-3-yl} acrylate (Methyl 2 - {(2 R *, 3 S * , 5 S *)-5-pentyl-2-phenethyl-tetrahydrofuran-3-yl} acrylate)
오토클레이브 플라스크에 Pd(PPh3)4(5.4mg, 5mol%)와 포타슘카보네이(K2CO3) (39.4mg, 0.282mol)를 첨가하였다. 그리고 메탄올(3mL)에 있는 (2R*,3R*,5S*)-3-(1-아이오도비닐)-5-펜틸-2-펜에틸-테트라히드로퓨란(37.8mg, 0.094mmol)을 첨가하였다. 그 후 혼합물을 CO가스하(200psi)에서 미리 70℃로 가열시킨 오일배스에서 3시간동안 반응하였다. 이 때에 휘발성 물질은 날려보낸 후에 실리카젤 크로마토그래피로 정제하여 하기 화학식으로 표시되는 화합물을 얻었다. To the autoclave flask was added Pd (PPh 3) 4 (5.4 mg, 5 mol%) and potassium carbonei (K 2 CO 3) (39.4 mg, 0.282 mol). And (2 R *, 3 R *, 5 S *)-3- (1-iodovinyl) -5-pentyl-2-phenethyl-tetrahydrofuran (37.8 mg, 0.094 mmol) in methanol (3 mL) Was added. Thereafter, the mixture was reacted for 3 hours in an oil bath which was previously heated to 70 ° C. under CO gas (200 psi). At this time, the volatiles were blown off and purified by silica gel chromatography to obtain a compound represented by the following formula.
수율 : 83% Yield: 83%
TLC, Rf : 0.38 (15:1, Hexanes/EtOAc) TLC, R f : 0.38 (15: 1, Hexanes / EtOAc)
IR (film)3021, 2949, 2855, 1720, 1602, 1205, 1054, 767, 695 cm-1 IR (film) 3021, 2949, 2855, 1720, 1602, 1205, 1054, 767, 695 cm -1
1H NMR (400 MHz, CDCl3) δ 7.22-7.27 (m, 2H), 7.12-7.17 (m, 3H), 1 H NMR (400 MHz, CDCl 3 ) δ 7.22-7.27 (m, 2H), 7.12-7.17 (m, 3H),
6.29 (s, 1H), 5.60 (s, 1H), 4.12-4.19 (m, 1H), 3.88-3.97 (m, 1H), 3.72 (s, 3H), 3.42-3.50 (m, 1H), 2.74-2.84 (m, 1H), 2.49-2.59 (m, 1H), 2.03-2.11 (m, 1H), 1.28-1.76 (m, 11H), 0.91 (t, J=6.9Hz, 3H) 6.29 (s, 1H), 5.60 (s, 1H), 4.12-4.19 (m, 1H), 3.88-3.97 (m, 1H), 3.72 (s, 3H), 3.42-3.50 (m, 1H), 2.74- 2.84 (m, 1H), 2.49-2.59 (m, 1H), 2.03-2.11 (m, 1H), 1.28-1.76 (m, 11H), 0.91 (t, J = 6.9 Hz, 3H)
13C NMR (125MHz, CDCl3) δ 170.2, 145.2, 142.2, 131.1, 130.9, 128.3, 81.7, 81.2, 54.6, 46.2, 39.2, 38.6, 37.3, 35.1, 34.6, 28.6, 25.3, 16.7, 2.6 13 C NMR (125 MHz, CDCl 3 ) δ 170.2, 145.2, 142.2, 131.1, 130.9, 128.3, 81.7, 81.2, 54.6, 46.2, 39.2, 38.6, 37.3, 35.1, 34.6, 28.6, 25.3, 16.7, 2.6
MS (ESI) m/z (rel intensity) 354 (M+Na+, 11), 331 (100), 330 (M+, 5), 281 (63) MS (ESI) m / z (rel intensity) 354 (M + Na + , 11), 331 (100), 330 (M + , 5), 281 (63)
Anal. Calcd for C21H30O3: C, 76.33; H, 9.15; O, 14.52. Found: C, 76.18 H, 9.32. Anal. Calcd for C 21 H 30 O 3 : C, 76.33; H, 9. 15; O, 14.52. Found: C, 76.18 H, 9.32.
[실시예 12] Example 12
(2R*,3S*,5S*)-3-에티닐-5-펜틸-2-펜에틸-테트라히드로퓨란((2R*,3S*,5S*)-3-Ethynyl-5-pentyl-2-phenethyl-tetrahydrofuran)의 제조 (2 R *, 3 S * , 5 S *) - 3-ethynyl-5-pentyl-2-phenethyl-tetrahydro-furan ((2 R *, 3 S *, 5 S *) - 3-Ethynyl- Preparation of 5-pentyl-2-phenethyl-tetrahydrofuran)
0℃에서 반응용기에 DMF (2.4ml)에 (2R*,3R*,5S*)-3-(1-아이오도비닐)-5-펜틸-2-펜에틸-테트라히드로퓨란(46mg, 0.116mmol)을 넣고 THF (0.2ml, 0.20mmol)에 있는 1.0M의 NaHMDS (sodium hexamethyldisilazide)를 5분 동안 천천히 첨가하였다. 그 후 5시간동안 반응하였다. 이 때에 물을 넣어 반응을 종결한 후에 EA로 추출한 후에 MgSO4로 건조시켰다. 용매를 감압증류한 후에 실리카젤 크로마토그래피로 정제하여 하기 화학식으로 표시되는 화합물을 얻었다. In a reaction vessel at 0 ℃ in DMF (2.4ml) (2 R * , 3 R *, 5 S *) - 3- (1- iodo-vinyl) -5-pentyl-2-phenethyl-tetrahydro-furan (46mg , 0.116 mmol) and 1.0 M NaHMDS (sodium hexamethyldisilazide) in THF (0.2 ml, 0.20 mmol) were added slowly for 5 minutes. After that, the reaction was carried out for 5 hours. At this time, water was added to terminate the reaction, followed by extraction with EA and drying with MgSO 4. The solvent was distilled under reduced pressure and purified by silica gel chromatography to obtain a compound represented by the following formula.
수율 : 90% Yield: 90%
TLC, Rf : 0.41 (15:1, Hexanes/EtOAc) TLC, R f : 0.41 (15: 1, Hexanes / EtOAc)
IR (film) 3298, 3026, 2958, 2152, 1605, 1080, 767, 702 cm-1 IR (film) 3298, 3026, 2958, 2152, 1605, 1080, 767, 702 cm -1
1H NMR (400MHz, CDCl3) δ 7.15-7.30 (m, 5H), 3.73-3.82 (m, 2H) 2.98-3.06 (m, 1H), 2.67-2.84 (m, 2H), 2.29-2.38 (m, 1H), 2.13 (d, J=2.7Hz, 1H), 1.98-2.06 (m, 2H), 1.25-1.73 (m, 8H), 0.89 (t, J = 6.9 Hz, 3H) 1 H NMR (400 MHz, CDCl 3 ) δ 7.15-7.30 (m, 5H), 3.73-3.82 (m, 2H) 2.98-3.06 (m, 1H), 2.67-2.84 (m, 2H), 2.29-2.38 (m , 1H), 2.13 (d, J = 2.7 Hz, 1H), 1.98-2.06 (m, 2H), 1.25-1.73 (m, 8H), 0.89 (t, J = 6.9 Hz, 3H)
13C NMR (125MHz, CDCl3) δ 131.1, 130.9, 128.4, 86.8, 81.9, 81.4, 73.8, 41.9, 38.8, 36.9, 36.3, 35.1, 34.6, 28.6, 25.3, 16.7, 2.6 13 C NMR (125 MHz, CDCl 3 ) δ 131.1, 130.9, 128.4, 86.8, 81.9, 81.4, 73.8, 41.9, 38.8, 36.9, 36.3, 35.1, 34.6, 28.6, 25.3, 16.7, 2.6
MS (ESI) m/z (rel. intensity) 271 (100), 270 (M+, 4), 155 (29) MS (ESI) m / z (rel. Intensity) 271 (100), 270 (M + , 4), 155 (29)
Anal. Calcd for C19H26O: C, 84.39; H, 9.69; O, 5.92. Found: C, 84.31 H, 9.92. Anal. Calcd for C 19 H 26 O: C, 84.39; H, 9.69; O, 5.92. Found: C, 84.31 H, 9.92.
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etrahedron Letters. 1993, 34, 6251-6254 |
Journal of American Chemical Society, 2001, 123, 2450-2451 |
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