KR101044277B1 - Bicyclo Furan Derivatives and the method for preparing the Same - Google Patents

Bicyclo Furan Derivatives and the method for preparing the Same Download PDF

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KR101044277B1
KR101044277B1 KR1020080082500A KR20080082500A KR101044277B1 KR 101044277 B1 KR101044277 B1 KR 101044277B1 KR 1020080082500 A KR1020080082500 A KR 1020080082500A KR 20080082500 A KR20080082500 A KR 20080082500A KR 101044277 B1 KR101044277 B1 KR 101044277B1
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nucleic acid
bicyclo
furan
tetrahydroisobenzofuran
tetrahydro
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오창호
이수진
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한양대학교 산학협력단
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    • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

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Abstract

본 발명은 하기 화학식 1로 표시되는 바이사이클로 퓨란 유도체 및 그 제조방법에 관한 것으로서, 본 발명에 따르면 금(Au)할로겐화물을 촉매로 하여 분자내의 연속적인 고리환원반응을 통해 단시간에 고수율로 삼각고리를 포함하는 바이사이클로 퓨란 유도체를 제조할 수 있다.The present invention relates to a bicyclo furan derivative represented by the following formula (1) and to a method for preparing the same, according to the present invention by using a gold (Au) halide as a catalyst through a tricyclic continuous ring reduction reaction in the molecule in a short time in high yield Bicyclo furan derivatives comprising a ring can be prepared.

Figure 112010077617733-pat00001
Figure 112010077617733-pat00001

(1)         (One)

(상기 식에서, A는 탄소원자, 질소원자 또는 산소원자이고, R1 내지 R7은 각각 독립적으로, 수소원자, C1~C10의 알킬기, 알콕시, 알킬기로 에스테르화된 카르복실기, C6~C10의 아릴기, 아릴옥시기이며, n은 1 내지 3의 정수임)(Wherein A is a carbon atom, a nitrogen atom or an oxygen atom, R 1 to R 7 are each independently a hydrogen atom, a C 1 to C 10 alkyl group, alkoxy, a carboxyl group esterified with an alkyl group, C 6 to C) 10 is an aryl group, an aryloxy group, n is an integer of 1 to 3)

바이사이클로 퓨란, 아자바이사이클로 퓨란, 금촉매 Bicyclo Furan, Azabicyclo Furan, Gold Catalyst

Description

삼각고리를 포함하는 바이사이클로 퓨란 유도체 및 그 제조 방법{Bicyclo Furan Derivatives and the method for preparing the Same}Bicyclo furan derivatives containing triangular ring and method for preparing the same {Bicyclo Furan Derivatives and the method for preparing the Same}

본 발명은 바이사이클로 퓨란 유도체 및 그 제조방법에 관한 것으로서, 더욱 상세하게는 향장 및 약학 원료로 사용될 수 있는 삼각고리를 포함하는 신규 바이사이클로 퓨란 유도체 및 금(Au)할로겐화물을 촉매로 하여 일단계의 분자내 연속적인 고리환원반응을 통해 단시간에 고수율로 상기 퓨란 유도체를 제조하는 방법에 관한 것이다.The present invention relates to a bicyclo furan derivative and a method for manufacturing the same, and more particularly, a novel bicyclo furan derivative including a triangular ring which can be used as a cosmetic and pharmaceutical raw materials, and a gold (Au) halide. It relates to a method for preparing the furan derivative in a high yield in a short time through the intramolecular continuous ring reduction reaction of.

생체 활성을 나타내는 다중고리 화합물은 의학 및 약학 분야에서 유용하게 사용되는 중요한 물질로서, 신약 개발의 전제로서 신규한 구조를 가진 다중 고리화합물의 개발의 필요성이 점차 높아지고 있다. 이 중에서 바이사이클로 화합물의 경우 치환기에 따라 쉽게 다양한 활성을 나타낼 수 있기 때문에 특히 그 응용성이 높다. Multicyclic compounds exhibiting biological activity are important materials useful in the medical and pharmaceutical fields, and as a premise for the development of new drugs, the need for the development of multicyclic compounds having a novel structure is gradually increasing. Among these, in the case of the bicyclo compound, since it can easily exhibit various activities depending on the substituent, its applicability is particularly high.

구체적으로 본 발명에 따른 화합물이 속하는 바이사이클로 퓨란 유도체는 향수의 원료로 사용되는 천연물 모노터펜과 구조가 유사하기 때문에 에센셜 오일로 사용할 수 있어 매우 유용하다. 또한 아민으로 치환된 아자바이사이클로 화합물의 약리학적 효과는 이미 널리 알려져 있다. 예를 들어, 아자바이사이클로 [3.1.0]핵산 화합물은 통증, 우울증, 불안장애, 식이장애 및 요실금 치료에 효과가 있다고 알려져 있으며(WO2007/127421 및 WO2008/024143), 당뇨병, 제2형 당뇨병인 전당뇨병, 신진대사 산성증, 포만 질환 또는 비만 치료제로도 응용되고 있다. 아자바이사이클로 [3.1.0]핵산 화합물은 이 밖에도 다양한 신진대사, 신경, 항염증 그리고 자기면역질환 같은 염증질환, 다발성 경화증, 류머티스 관절염, 바이러스, 암, 위장 장애의 억제제로 사용할 수 있으며, 다낭성난소증후군으로 발생하는 불임 치료에도 사용되고 있다(WO 2007/029086).Specifically, the bicyclo furan derivative to which the compound according to the present invention belongs is very useful because it can be used as an essential oil because its structure is similar to that of a natural monoterpene used as a raw material of perfume. In addition, the pharmacological effects of azabicyclo compounds substituted with amines are well known. For example, azabicyclo [3.1.0] nucleic acid compounds are known to be effective in the treatment of pain, depression, anxiety disorders, eating disorders and incontinence (WO2007 / 127421 and WO2008 / 024143). It is also applied as a treatment for pre-diabetes, metabolic acidosis, satiety disease or obesity. Azabicyclo [3.1.0] nucleic acid compounds can be used as an inhibitor of various metabolic, neurological, anti-inflammatory and autoimmune diseases, as well as multiple sclerosis, rheumatoid arthritis, viruses, cancer and gastrointestinal disorders. It is also used to treat infertility caused by the syndrome (WO 2007/029086).

이와 같이 바이사이클로 화합물은 약학 또는 향장 원료로 그 효능이 널리 알려져 있기 때문에 이를 효과적으로 합성하는 방법에 대한 많은 연구가 진행되어 왔다. 비교적 최근의 연구 결과로서, Kouichi Ohe와 Sakae Uemura에 의해 전이금속착물을 촉매로 이용하여 퓨란 중간체를 생성한 후, 이분자 반응을 통해 삼각고리 화합물을 합성하는 방법이 제안되었으나(J.Org.Chem.2004.69.1557.Catalytic Cyclopropanation of Alkenes of via (2-Furyl)carbene Complexes from 1-Benzoyl-cis-buten-3-yne with Transition Metal Compounds, 2004/02/05 / Org.Lett.2003.5,2619.Doyle-Kirmse Reaction of Allylic Sulfides with Diazoalkane-Free (2-Furyl)carbenoid Transfer), 촉매를 사용하여 퓨란 중간체를 생성한 후 2차 반응 과정을 통해 삼각고리를 포함하는 퓨란 유도체를 제조하는 방법은 단계가 복잡하고 시간이 많이 소요되며 수율이 낮고 제조 비용이 높은 단점이 있어서, 보다 효율적인 합성 방법이 요구되어 왔다. As described above, since the bicyclo compound is widely known as a pharmaceutical or cosmetic ingredient, much research has been conducted on how to effectively synthesize the bicyclo compound. As a result of a relatively recent study, a method has been proposed by Kouichi Ohe and Sakae Uemura to generate a furan intermediate using a transition metal complex as a catalyst, and then synthesize a tricyclic compound through a bimolecular reaction (J. Org. Chem. Catalytic Cyclopropanation of Alkenes of via (2-Furyl) carbene Complexes from 1-Benzoyl-cis-buten-3-yne with Transition Metal Compounds, 2004/02/05 / Org. Lett. 2003.5,2619.Doyle- Kirmse Reaction of Allylic Sulfides with Diazoalkane-Free (2-Furyl) carbenoid Transfer), a method of preparing furan derivatives containing triangular rings through secondary reaction process after producing furan intermediate using catalyst Due to the time-consuming, low yield and high manufacturing cost, a more efficient synthesis method has been required.

본 발명이 해결하고자 하는 첫 번째 과제는 하기 화학식 (1)로 표시되는 삼각고리를 포함하는 바이사이클로 퓨란 유도체를 제공하는 것이다: The first problem to be solved by the present invention is to provide a bicyclo furan derivative comprising a triangular ring represented by the formula (1):

Figure 112008060045355-pat00002
Figure 112008060045355-pat00002

(1)     (One)

상기 식에서, A는 탄소원자, 질소원자 또는 산소원자이고(A가 질소원자일 때, R3는 없고, A가 산소일 때, R2 및 R3는 없음), R1 내지 R7은 각각 독립적으로, 수소원자, C1~C10의 알킬기, 알콕시, 알킬기로 에스테르화된 카르복실기, C6~C10의 아릴기, 아릴옥시기이며, n은 1 내지 3의 정수이다. Wherein A is a carbon atom, a nitrogen atom or an oxygen atom (when A is a nitrogen atom, there is no R 3 , and when A is oxygen, there is no R 2 and R 3 ), and R 1 To R 7 are each independently a hydrogen atom, a C 1 to C 10 alkyl group, alkoxy, a carboxyl group esterified with an alkyl group, a C 6 to C 10 aryl group, an aryloxy group, and n is an integer of 1 to 3 .

본 발명이 해결하고자 하는 두 번째 과제는 금(Au)할로겐화물을 촉매로 이용하여 하기 반응식 1에 따라 일단계의 연속적인 고리 환원반응을 통해 하기 화학식 (2)의 화합물로부터 삼각고리를 포함하는 화학식 (1)의 바이사이클로 퓨란 유도체를 제조하는 방법을 제공하는 것이다:The second problem to be solved by the present invention is a chemical formula comprising a tricyclic ring from the compound of the formula (2) through a one-step continuous ring reduction reaction according to Scheme 1 using a gold (Au) halide as a catalyst It is to provide a method for producing the bicyclo furan derivative of (1):

반응식 1Scheme 1

Figure 112010077617733-pat00033
Figure 112010077617733-pat00033

(2) (1)              (2) (1)

상기 식에서, A, R1 내지 R7 및 n은 상기 화학식 1에서 정의한 바와 같다. In the above formula, A, R 1 To R 7 and n are as defined in the formula (1).

상기 첫 번째 과제를 해결하기 위하여, 본 발명은 하기 화학식 (1)로 표시되는 삼각고리를 포함하는 바이사이클로 퓨란 유도체를 제공한다: In order to solve the first problem, the present invention provides a bicyclo furan derivative comprising a triangular ring represented by the following formula (1):

Figure 112008060045355-pat00004
Figure 112008060045355-pat00004

(1)      (One)

상기 식에서, A는 탄소원자, 질소원자 또는 산소원자이고(A가 질소원자일 때, R3는 없고, A가 산소일 때, R2 및 R3는 없음), R1 내지 R7은 각각 독립적으로, 수소원자, C1~C10의 알킬기, 알콕시, 알킬기로 에스테르화된 카르복실기, C6~C10의 아릴기, 아릴옥시기이며, n은 1 내지 3의 정수이다. Wherein A is a carbon atom, a nitrogen atom or an oxygen atom (when A is a nitrogen atom, there is no R 3 , and when A is oxygen, there is no R 2 and R 3 ), and R 1 To R 7 are each independently a hydrogen atom, a C 1 to C 10 alkyl group, alkoxy, a carboxyl group esterified with an alkyl group, a C 6 to C 10 aryl group, an aryloxy group, and n is an integer of 1 to 3 .

본 발명의 일 실시예에 의하면, 상기 삼각고리를 포함하는 바이사이클로 퓨 란 유도체는 1-(2-(벤질옥시)-3,3-디메틸바이사이클로[3.1.0]핵산-1-일)-4,5,6,7-테트라하이드로아이소벤조퓨란; 1-(2-(벤질옥시)-3,3-디메틸바이사이클로[3.1.0]핵산-1-일)-5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란; 1-(2-(벤질옥시)-4,4-디메틸바이사이클로[3.1.0]핵산-1-일)-4,5,6,7-테트라하이드로아이소벤조퓨란; 1-(2-(벤질옥시)-4,4-디메틸바이사이클로[3.1.0]핵산-1-일)-5,6,7,8-테트라하이드로-4H-사이클로햅타퓨란; 1-(2-(벤질옥시)바이사이클로[3.1.0]핵산-1-일)-4,5,6,7-테트라하이드로아이소벤조퓨란; 1-(2-(벤질옥시)바이사이클로[3.1.0]핵산-1-일)-5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란; tert-부틸디메틸(1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-2-일옥시)실란; tert-부틸(3,3-디메틸-1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-2-일옥시)디메틸실란; 1-메틸-5-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산; 1-메틸-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산; 1-페닐-5-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산; 1-페닐-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산; 3,6-디페닐-1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)-3-아자바이사이클로[3.1.0]핵산; 3,6-디페닐-1-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)-3-아자바이사이클로[3.1.0]핵산; 디에틸-1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실레이트; 디에틸-1-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)바이사 이클로[3.1.0]핵산-3,3-디카복실레이트; 디에틸-1-(4,5,6,7,8,9-핵사하이드로사이클로옥타[c]퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실레이트; 디에틸-1-페닐-5-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실레이트; 디에틸 1-페닐-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카르복실에이트; 1-(6-페닐-3-옥사바이사이클로[3.1.0]핵산-1-일)-(4,5,6,7-테트라하이드로아이소벤조퓨란로 구성된 군 중에서 선택될 수 있다. According to an embodiment of the present invention, the bicyclo furan derivative including the triangular ring is 1- (2- (benzyloxy) -3,3-dimethylbicyclo [3.1.0] nucleic acid-1-yl)- 4,5,6,7-tetrahydroisobenzofuran; 1- (2- (benzyloxy) -3,3-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -5,6,7,8-tetrahydro-4H-cyclohapta [ c ] furan; 1- (2- (benzyloxy) -4,4-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -4,5,6,7-tetrahydroisobenzofuran; 1- (2- (benzyloxy) -4,4-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -5,6,7,8-tetrahydro-4H-cyclohaptafuran; 1- (2- (benzyloxy) bicyclo [3.1.0] nucleic acid-1-yl) -4,5,6,7-tetrahydroisobenzofuran; 1- (2- (benzyloxy) bicyclo [3.1.0] nucleic acid-1-yl) -5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan; tert-butyldimethyl (1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid-2-yloxy) silane; tert-butyl (3,3-dimethyl-1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid-2-yloxy) dimethylsilane; 1-methyl-5- (4,5,6,7-tetrahydroisobenzofuran-1-yl) -3-tosyl-3-azabicyclo [3.1.0] nucleic acid; 1-methyl-5- (5,6,7,8-tetrahydro-4H-cyclohaptafuran-1-yl) -3-tosyl-3-azabicyclo [3.1.0] nucleic acid; 1-phenyl-5- (4,5,6,7-tetrahydroisobenzofuran-1-yl) -3-tosyl-3-azabicyclo [3.1.0] nucleic acid; 1-phenyl-5- (5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan-1-yl) -3-tosyl-3-azabicyclo [3.1.0] nucleic acid; 3,6-diphenyl-1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) -3-azabicyclo [3.1.0] nucleic acid; 3,6-diphenyl-1- (5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan-1-yl) -3-azabicyclo [3.1.0] nucleic acid; Diethyl-1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxylate; Diethyl-1- (5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxylate; Diethyl-1- (4,5,6,7,8,9-nucleushydrocycloocta [ c ] furan-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxylate; Diethyl-1-phenyl-5- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxylate; Diethyl 1-phenyl-5- (5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxyl Eight; It can be selected from the group consisting of 1- (6-phenyl-3-oxabicyclo [3.1.0] nucleic acid-1-yl)-(4,5,6,7-tetrahydroisobenzofuran.

상기 두 번째 과제를 해결하기 위하여, 본 발명은 금(Au)할로겐화물을 촉매로 이용하여 하기 반응식 1에 따라 일단계로 이루어지는 연속적인 고리 환원반응을 통해 하기 화학식 (2)의 화합물로부터 삼각고리를 포함하는 화학식 (1)의 바이사이클로 퓨란 유도체를 제조하는 방법을 제공한다:In order to solve the second problem, the present invention by using a gold (Au) halide as a catalyst to the tricyclic ring from the compound of formula (2) through a continuous ring reduction reaction consisting of one step according to Scheme 1 below Provided is a method of preparing a bicyclo furan derivative of formula (1) comprising:

반응식 1Scheme 1

Figure 112010077617733-pat00034
Figure 112010077617733-pat00034

(2) (1)                (2) (1)

상기 식에서, A는 탄소원자, 질소원자 또는 산소원자이고(A가 질소원자일 때, R3는 없고, A가 산소일 때, R2 및 R3는 없음), R1 내지 R7은 각각 독립적으로, 수소원자, C1~C10의 알킬기, 알콕시, 알킬기로 에스테르화된 카르복실기, C6~C10의 아릴 기, 아릴옥시기이며, n은 1 내지 3의 정수이다.Wherein A is a carbon atom, a nitrogen atom or an oxygen atom (when A is a nitrogen atom, there is no R 3 , and when A is oxygen, there is no R 2 and R 3 ), and R 1 To R 7 are each independently a hydrogen atom, a C 1 to C 10 alkyl group, alkoxy, a carboxyl group esterified with an alkyl group, a C 6 to C 10 aryl group, an aryloxy group, n is an integer of 1 to 3 .

본 발명의 일 실시예에 의하면, 상기 화학식 (2)의 화합물은 하기 반응식 2에 따라 화학식 (3)의 화합물과 화학식 (4)의 화합물의 반응에 의해 제조될 수 있다:According to an embodiment of the present invention, the compound of formula (2) may be prepared by the reaction of a compound of formula (3) with a compound of formula (4) according to Scheme 2:

반응식 2Scheme 2

Figure 112008060045355-pat00006
Figure 112008060045355-pat00006

(3) (4) (2)        (3) (4) (2)

상기 식에서, A 및 R1 내지 R7은 반응식 1에서 정의된 바와 같다.Wherein A and R 1 To R 7 are as defined in Scheme 1.

한편, 본 발명의 다른 일 실시예에 의하면 상기 반응식 1에서 촉매로 사용되는 금(Au)할로겐화물은 골드(Ⅲ)브로마이드(AuBr3)인 것이 바람직하다. On the other hand, according to another embodiment of the present invention, the gold (Au) halide used as the catalyst in Scheme 1 is preferably gold (III) bromide (AuBr 3 ).

본 발명에 따라 금(Au)할로겐화물을 촉매로 이용하여 바이사이클로 퓨란 유도체를 제조하면, 일단계의 분자내 연속적인 고리환원반응을 통해 단시간에 고수율로 삼각고리를 포함하는 바이사이클로 퓨란 유도체를 제조할 수 있으며, 이에 따라 제조된 삼각고리를 포함하는 바이사이클로 퓨란 유도체는 향장 또는 약학 분야의 신규 원료로서 유용하게 사용될 수 있다.According to the present invention, when a bicyclo furan derivative is prepared using a gold (Au) halide as a catalyst, a bicyclo furan derivative including a tricyclic ring in a high yield in a short time through a single intramolecular continuous ring reduction reaction is produced. The bicyclo furan derivative including the triangular ring thus prepared may be usefully used as a novel raw material in cosmetic or pharmaceutical fields.

이하에서 본 발명을 더욱 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.

본 발명에 따른 삼각고리를 포함하는 바이사이클로 퓨란 유도체는 하기 화학식 (1)로 표시된다.The bicyclo furan derivative including the triangular ring according to the present invention is represented by the following formula (1).

Figure 112008060045355-pat00007
Figure 112008060045355-pat00007

(1)      (One)

상기 식에서, A는 탄소원자, 질소원자 또는 산소원자이고(A가 질소원자일 때, R3는 없고, A가 산소일 때, R2 및 R3는 없음), R1 내지 R7은 각각 독립적으로, 수소원자, C1~C10의 알킬기, 알콕시, 알킬기로 에스테르화된 카르복실기, C6~C10의 아릴기, 아릴옥시기이며, n은 1 내지 3의 정수이다.Wherein A is a carbon atom, a nitrogen atom or an oxygen atom (when A is a nitrogen atom, there is no R 3 , and when A is oxygen, there is no R 2 and R 3 ), and R 1 To R 7 are each independently a hydrogen atom, a C 1 to C 10 alkyl group, alkoxy, a carboxyl group esterified with an alkyl group, a C 6 to C 10 aryl group, an aryloxy group, and n is an integer of 1 to 3 .

상기 삼각고리를 포함하는 화학식 (1)의 바이사이클로 퓨란 유도체는 금(Au)할로겐화물을 촉매로 이용하여 하기 반응식 1에 따라 일단계의 연속적인 고리 환원반응을 통해 화학식 2에 의한 화합물로부터 제조될 수 있다:Bicyclo furan derivative of formula (1) comprising the triangular ring is prepared from the compound according to formula (2) through a one-step continuous ring reduction reaction according to Scheme 1 using gold (Au) halide as a catalyst Can:

Figure 112010077617733-pat00035
Figure 112010077617733-pat00035

(2) (1)            (2) (1)

상기 식에서, A, R1 내지 R7 및 n은 상기 화학식 1에서 정의한 바와 같다. In the above formula, A, R 1 To R 7 and n are as defined in the formula (1).

또한 상기 반응식 1의 출발 물질로 사용되는 화학식 (2)의 화합물은 하기 반응식 2에 따라 화학식 (3)의 화합물과 화학식 (4)의 화합물의 반응에 의해 제조될 수 있다.In addition, the compound of formula (2) to be used as the starting material of Scheme 1 may be prepared by the reaction of the compound of formula (3) and the compound of formula (4) according to the following scheme 2.

Figure 112008060045355-pat00009
Figure 112008060045355-pat00009

(3) (4) (2)        (3) (4) (2)

상기 식에서, A, R1 내지 R7 및 n은 상기 화학식 1에서 정의한 바와 같다. In the above formula, A, R 1 To R 7 and n are as defined in the formula (1).

한편 상기 반응식 1에서 촉매로 사용되는 금(Au)할로겐화물은 골드(Ⅲ)브로마이드(AuBr3)인 것이 바람직하다. On the other hand, the gold (Au) halide used as the catalyst in Scheme 1 is preferably gold (III) bromide (AuBr 3 ).

이하, 바람직한 실시예를 들어 본 발명을 더욱 상세하게 설명하지만, 본 발명이 이에 의해 제한되는 것은 아니다. Hereinafter, the present invention will be described in more detail with reference to preferred examples, but the present invention is not limited thereto.

실시예Example 1:  One: 1-(2-(1- (2- ( 벤질옥시Benzyloxy )-3,3-) -3,3- 디메틸바이사이클로[3.1.0]핵산Dimethylbicyclo [3.1.0] nucleic acid -1-일)-4,5,6,7-테-1-yl) -4,5,6,7-te 트라하이드로아이소Trahydroiso 벤조퓨란Benzofuran

Figure 112008060045355-pat00010
Figure 112008060045355-pat00010

시험관에 2-(3-(벤질옥시)-4,4-디메틸햅트-6-앤-1-아이닐)사이클로핵스-1-앤카바알데히드(50 mg, 0.148 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(1.9mg, 0.004 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 15분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 1-(2-(벤질옥시)-3,3-디메틸바이사이클로[3.1.0]핵산-1-일)-4,5,6,7-테트라하이드로아이소벤조퓨란 40 mg(80 %)를 얻었다.In vitro, 2- (3- (benzyloxy) -4,4-dimethylhapt-6-an-1-ynyl) cyclonux-1-ancarbaaldehyde (50 mg, 0.148 mmol) was added to toluene (1 mL). After melting, a magnetic spoon was put. Then, gold (III) bromide (1.9 mg, 0.004 mmol) was added at 0 ° C., and the test tube was filled with argon, followed by sealing with a rubber diaphragm. Then stirred at room temperature for 15 minutes. The solvent was then removed by vacuum distillation and then column chromatography to give the product 1- (2- (benzyloxy) -3,3-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -4,5,6 40 mg (80%) of 7-tetrahydroisobenzofuran was obtained.

FT-IR(neat, cm-1) 2931, 2860, 1558, 1453, 1100, 1073, 1027 1H-NMR (400MHz, CDCl3) δ 7.31~7.42 (m, 5H), 7.02(s, 1H), 4.52 (ABq, Δδ = 142.0Hz, J = 12Hz, 2H), 3.79 (s, 1H), 2.51 (bs, 4H), 1.84~1.75 (m, 1H), 1.66 (bs, 4H), 1.47 (d, J = 10.4Hz, 2H), 1.21~1.19 (m, 2H), 1.16 (s, 3H), 1.00 (s, 3H) 13C- NMR (100MHz, CDCl3) δ 151.04, 140.09, 135.65, 128.80, 127.92, 127.72, 122.79, 116.38, 90.85, 70.69, 49.843, 43.87, 33.824, 30.43, 27.29, 24.25, 24.12, 23.79, 22.32, 21.39, 21.10 HRMS (EI) calculated for C17H20O 336.2089 found, 336.2087.FT-IR (neat, cm -1 ) 2931, 2860, 1558, 1453, 1100, 1073, 1027 1 H-NMR (400 MHz, CDCl 3 ) δ 7.31-7.42 (m, 5H), 7.02 (s, 1H), 4.52 (ABq, Δ δ = 142.0 Hz, J = 12 Hz, 2H), 3.79 (s, 1H), 2.51 (bs, 4H), 1.84-1.75 (m, 1H), 1.66 (bs, 4H), 1.47 (d , J = 10.4 Hz, 2H), 1.21-1.19 (m, 2H), 1.16 (s, 3H), 1.00 (s, 3H) 13 C- NMR (100 MHz, CDCl 3 ) δ 151.04, 140.09, 135.65, 128.80, 127.92, 127.72, 122.79, 116.38, 90.85, 70.69, 49.843, 43.87, 33.824, 30.43, 27.29, 24.25, 24.12, 23.79, 22.32, 21.39, 21.10 HRMS (EI) calculated for C 17 H 20 O 336.2089 found, 336.2087.

실시예Example 2:  2: 1-(2-(1- (2- ( 벤질옥시Benzyloxy )-3,3-) -3,3- 디메틸바이사이클로[3.1.0]핵산Dimethylbicyclo [3.1.0] nucleic acid -1-일)-5,6,7,8-테-1-yl) -5,6,7,8-te 트라Tra 하이드로-4H-Hydro-4H- 사이클로햅타[Cyclohapta [ cc ]퓨란Furan

Figure 112008060045355-pat00011
Figure 112008060045355-pat00011

시험관에 2-(3-(벤질옥시)-4,4-디메틸햅트-6-앤-1-아이닐)사이클로햅트-1-앤카바알데히드(50 mg, 0.141 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(3.0mg, 0.007 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 0℃에서 10분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 1-(2-(벤질옥시)-3,3-디메틸바이사이클로[3.1.0]핵산-1-일)-5,6,7,8-테트라하이드로-4H-사이클로햅타퓨란 42.5 mg(85 %)를 얻었다.In vitro, 2- (3- (benzyloxy) -4,4-dimethylhapt-6-and-1-ynyl) cyclohap-1-ancarbaaldehyde (50 mg, 0.141 mmol) was added to toluene (1 mL). After melting, a magnetic spoon was put. Then, gold (III) bromide (3.0 mg, 0.007 mmol) was added at 0 ° C., and the test tube was filled with argon, followed by sealing with a rubber septum. Then, it stirred at 0 degreeC for 10 minutes. The solvent was then removed by vacuum distillation and then column chromatography to give the product 1- (2- (benzyloxy) -3,3-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -5,6,7 42.5 mg (85%) of 8-tetrahydro-4H-cyclohaptafuran was obtained.

FT-IR(neat, cm-1) 2921, 2850, 1762, 1604, 1448, 1363, 1127, 1074, 1028; 1H-NMR (400MHz, CDCl3) δ 7.20~7.23 (m, 5H), 7.00 (s, 1H), 4.52 (ABq, Δδ = 147.2Hz, J = 12.4Hz, 2H), 3.72 (s, 1H), 6.2.60~2.45 (m, 4H), 1.89~1.84 (m, 1H), 1.78~1.74 (m, 2H), 1.68~1.51 (m, 6H), 1.30 (t, J = 4.4Hz, 1H), 1.18 (s, 3H), 1.12~1.09 (m, 1H), 1.00 (s, 3H); 13C-NMR (100MHz, CDCl3) δ 151.72, 139.41, 135.47, 128.11, 127.15, 127.02, 122.65, 91.35, 70.36, 47.78, 43.15, 32.83, 30.27, 29.73, 29.23, 25.97, 25.90, 25.73, 24.01, 19.92; HRMS (EI) calculated for C24 H30O2 350.2246 found,350.2250.FT-IR (neat, cm −1 ) 2921, 2850, 1762, 1604, 1448, 1363, 1127, 1074, 1028; 1 H-NMR (400 MHz, CDCl 3 ) δ 7.20-7.23 (m, 5H), 7.00 (s, 1H), 4.52 (ABq, Δ δ = 147.2 Hz, J = 12.4 Hz, 2H), 3.72 (s, 1H ), 6.2.60-2.45 (m, 4H), 1.89-1.84 (m, 1H), 1.78-1.74 (m, 2H), 1.68-1.51 (m, 6H), 1.30 (t, J = 4.4 Hz, 1H ), 1.18 (s, 3H), 1.12-1.09 (m, 1H), 1.00 (s, 3H); 13 C-NMR (100 MHz, CDCl 3 ) δ 151.72, 139.41, 135.47, 128.11, 127.15, 127.02, 122.65, 91.35, 70.36, 47.78, 43.15, 32.83, 30.27, 29.73, 29.23, 25.97, 25.90, 25.73, 24.01, 19.92 ; HRMS (EI) calculated for C 24 H 30 O 2 350.2246 found, 350.2250.

실시예Example 3:  3: 1-(2-(1- (2- ( 벤질옥시Benzyloxy )-4,4-) -4,4- 디메틸바이사이클로[3.1.0]핵산Dimethylbicyclo [3.1.0] nucleic acid -1-일)-4,5,6,7-테-1-yl) -4,5,6,7-te 트라하이드로아이소Trahydroiso 벤조퓨란Benzofuran

Figure 112008060045355-pat00012
Figure 112008060045355-pat00012

시험관에 2-(3-(벤질옥시)-5,5-디메틸햅트-6-앤-1-아이닐)사이클로핵스-1-앤카바알데히드(40 mg, 0.118 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.5mg, 0.005 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 0℃에서 15분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성 물 1-(2-(벤질옥시)-4,4-디메틸바이사이클로[3.1.0]핵산-1-일)-4,5,6,7-테트라하이드로아이소벤조퓨란 12 mg(30 %)를 얻었다.In vitro, 2- (3- (benzyloxy) -5,5-dimethylhapt-6-&-1-ynyl) cyclonux-1-ancarbaaldehyde (40 mg, 0.118 mmol) was added to toluene (1 mL). After melting, a magnetic spoon was put. Then, gold (III) bromide (2.5 mg, 0.005 mmol) was added at 0 ° C, and the test tube was filled with argon, followed by sealing with a rubber septum. Then, it stirred at 0 degreeC for 15 minutes. The solvent was then removed by vacuum distillation followed by column chromatography to give the product 1- (2- (benzyloxy) -4,4-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -4,5, 12 mg (30%) of 6,7-tetrahydroisobenzofuran was obtained.

FT-IR(neat, cm-1) 2932, 2862, 1758, 1684, 1453, 1364, 1095 1H-NMR (400MHz, CDCl3) δ 7.27~7.18 (m, 5H), 7.03 (s, 1H), 4.47 (t, J = 8.4Hz, 1H), 4.40 (ABq, Δδ = 48.4Hz, J = 12.0Hz, 2H), 2.57~2.41 (m, 4H), 1.30 (m, 1H), 1.18 (m, 1H), 1.14 (s, 3H), 1.00 (s, 3H) 13C-NMR (100MHz, CDCl3) δ 149.37, 139.02, 134.86, 128.15, 127.55, 127.22, 122.28, 116.97, 81.91, 71.27, 41.47, 37.04, 36.72, 29.93, 29.30, 26.34, 23.45, 23.19, 21.09, 20.40, 10.11 HRMS (EI) calculated for C24 H30O2 336.2089 found,336.2083.FT-IR (neat, cm -1 ) 2932, 2862, 1758, 1684, 1453, 1364, 1095 1 H-NMR (400 MHz, CDCl 3 ) δ 7.27 ~ 7.18 (m, 5H), 7.03 (s, 1H), 4.47 (t, J = 8.4 Hz, 1H), 4.40 (ABq, Δ δ = 48.4 Hz, J = 12.0 Hz, 2H), 2.57-2.41 (m, 4H), 1.30 (m, 1H), 1.18 (m, 1H), 1.14 (s, 3H), 1.00 (s, 3H) 13 C-NMR (100 MHz, CDCl 3 ) δ 149.37, 139.02, 134.86, 128.15, 127.55, 127.22, 122.28, 116.97, 81.91, 71.27, 41.47, 37.04 , 36.72, 29.93, 29.30, 26.34, 23.45, 23.19, 21.09, 20.40, 10.11 HRMS (EI) calculated for C 24 H 30 O 2 336.2089 found, 336.2083.

실시예Example 4:  4: 1-(2-(1- (2- ( 벤질옥시Benzyloxy )-4,4-) -4,4- 디메틸바이사이클로[3.1.0]핵산Dimethylbicyclo [3.1.0] nucleic acid -1-일)-5,6,7,8-테-1-yl) -5,6,7,8-te 트라Tra 하이드로-4H-Hydro-4H- 사이클로햅타[Cyclohapta [ cc ]퓨란Furan

Figure 112008060045355-pat00013
Figure 112008060045355-pat00013

시험관에 2-(3-(벤질옥시)-5,5-디메틸햅트-6-앤-1-아이닐)사이클로햅트-1-앤카바알데히드(55 mg, 0.156 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(3.4mg, 0.007 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 0℃에서 15분간 교반하였 다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 1-(2-(벤질옥시)-4,4-디메틸바이사이클로[3.1.0]핵산-1-일)-5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란 30 mg (56 %)를 얻었다.In vitro, 2- (3- (benzyloxy) -5,5-dimethylhapt-6-an-1-ynyl) cyclohap-1-ancarbaaldehyde (55 mg, 0.156 mmol) was added to toluene (1 mL). After melting, a magnetic spoon was put. Then, gold (III) bromide (3.4 mg, 0.007 mmol) was added at 0 ° C, and the test tube was filled with argon, followed by sealing with a rubber septum. Thereafter, the mixture was stirred at 0 ° C. for 15 minutes. The solvent was then removed by vacuum distillation and then column chromatography to give the product 1- (2- (benzyloxy) -4,4-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -5,6,7 30 mg (56%) of, 8-tetrahydro-4H-cyclohapta [ c ] furan were obtained.

FT-IR(neat, cm-1) 2921, 2831, 1563, 1449, 1364, 1342, 1098 1H-NMR (400MHz, CDCl3) δ 7.29~7.17 (m, 5H), 7.01 (s, 1H), 4.40 (ABq, Δδ = 51.2Hz, J = 12.0Hz, 2H), 4.36 (t, J = 8.4Hz, 1H), 2.59 (td, J = 8Hz, 2H), 2.47 (m, 2H), 1.74 (m, 4H), 1.60 (m, 4H), 1.29~1.26 (m, 1H), 1.21 (t, J = 5.2Hz, 1H), 1.17 (s, 3H), 1.15~1.12 (m, 1H), 1.00 (s, 3H), 0.89 (m, 1H) 13C-NMR (100MHz, CDCl3) δ 150.77, 139.02, 135.46, 128.23, 128.15, 127.40, 127.17, 123.66, 82.85, 71.31, 41.64, 36.97, 36.07, 32.84, 29.87, 29.83, 28.76, 26.46, 26.04, 25.64, 10.84 HRMS (EI) calculated for C24 H30O2 350.2246 found, 350.2249.FT-IR (neat, cm -1 ) 2921, 2831, 1563, 1449, 1364, 1342, 1098 1 H-NMR (400 MHz, CDCl 3 ) δ 7.29 ~ 7.17 (m, 5H), 7.01 (s, 1H), 4.40 (ABq, Δ δ = 51.2 Hz, J = 12.0 Hz, 2H), 4.36 (t, J = 8.4 Hz, 1H), 2.59 (td, J = 8 Hz, 2H), 2.47 (m, 2H), 1.74 ( m, 4H), 1.60 (m, 4H), 1.29-1.26 (m, 1H), 1.21 (t, J = 5.2 Hz, 1H), 1.17 (s, 3H), 1.15-1.12 (m, 1H), 1.00 (s, 3H), 0.89 (m, 1H) 13 C-NMR (100 MHz, CDCl 3 ) δ 150.77, 139.02, 135.46, 128.23, 128.15, 127.40, 127.17, 123.66, 82.85, 71.31, 41.64, 36.97, 36.07, 32.84 , 29.87, 29.83, 28.76, 26.46, 26.04, 25.64, 10.84 HRMS (EI) calculated for C 24 H 30 O 2 350.2246 found, 350.2249.

실시예Example 5 :  5: 1-(2-(1- (2- ( 벤질옥시Benzyloxy )) 바이사이클로Bicyclo [3.1.0]핵산-1-일)-4,5,6,7-[3.1.0] nucleic acid-1-yl) -4,5,6,7- 테트라하이드로아이소벤조퓨란Tetrahydroisobenzofuran

Figure 112008060045355-pat00014
Figure 112008060045355-pat00014

시험관에 2-(3-(벤질옥시)햅트-6-앤-1-아이닐)사이클로핵스-1-앤카바알데히드(35 mg, 0.113 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(1.7mg, 0.005 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 0℃에서 15분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 1-(2-(벤질옥시)바이사이클로[3.1.0]핵산-1-일)-4,5,6,7-테트라하이드로아이소벤조퓨란 4.5 mg (12 %)를 얻었다.Dissolve 2- (3- (benzyloxy) hapt-6-&-1-ynyl) cyclonux-1-ancarbaaldehyde (35 mg, 0.113 mmol) in toluene (1 mL) in a test tube and remove the magnetic stir bar. Put in. Then, gold (III) bromide (1.7 mg, 0.005 mmol) was added at 0 ° C, and the test tube was filled with argon, followed by sealing with a rubber septum. Then, it stirred at 0 degreeC for 15 minutes. The solvent was then removed via vacuum distillation and then column chromatography to give the product 1- (2- (benzyloxy) bicyclo [3.1.0] nucleic acid-1-yl) -4,5,6,7-tetrahydroiso 4.5 mg (12%) of benzofuran were obtained.

FT-IR(neat, cm-1) 2930, 2862, 1452, 1340, 1102, 1072, 1028 1H-NMR (400MHz, CDCl3) δ 7.29~7.19 (m, 5H), 7.02 (s, 1H), 4.43 (ABq, Δδ = 51.0Hz, J = 12.0Hz, 2H), 4.45 (t, J = 7.6Hz, 1H), 2.55~2.41 (m, 4H), 1.93 (m, 2H), 1.79 (m, 1H), 1.65 (q, 2H), 1.50 (m, 1H), 1.32 (m, 2H), 1.20 (t, J = 4.8Hz, 1H), 1.05 (m, 1H) 13C-NMR (100MHz, CDCl3) δ 149.36, 138.97, 134.80, 128.15, 127.62, 127.25, 122.29, 117.27, 82.97, 71.36, 28.90, 27.26, 24.82, 24.66, 23.43, 23.22, 20.97, 20.36, 10.42 HRMS (EI) calculated for C22 H26O2 308.1776 found, 308. 1772.FT-IR (neat, cm -1 ) 2930, 2862, 1452, 1340, 1102, 1072, 1028 1 H-NMR (400 MHz, CDCl 3 ) δ 7.29-7.19 (m, 5H), 7.02 (s, 1H), 4.43 (ABq, Δ δ = 51.0 Hz, J = 12.0 Hz, 2H), 4.45 (t, J = 7.6 Hz, 1H), 2.55-2.41 (m, 4H), 1.93 (m, 2H), 1.79 (m, 1H), 1.65 (q, 2H), 1.50 (m, 1H), 1.32 (m, 2H), 1.20 (t, J = 4.8 Hz, 1H), 1.05 (m, 1H) 13 C-NMR (100 MHz, CDCl 3 ) δ 149.36, 138.97, 134.80, 128.15, 127.62, 127.25, 122.29, 117.27, 82.97, 71.36, 28.90, 27.26, 24.82, 24.66, 23.43, 23.22, 20.97, 20.36, 10.42 HRMS (EI) calculated for C 22 H 26 0 2 308.1776 found, 308. 1772.

실시예Example 6:  6: 1-(2-(1- (2- ( 벤질옥시Benzyloxy )) 바이사이클로Bicyclo [3.1.0]핵산-1-일)-5,6,7,8-[3.1.0] nucleic acid-1-yl) -5,6,7,8- 테트라하이드로Tetrahydro -4-4 HH -- 사이클로햅타[Cyclohapta [ cc ]퓨란Furan

Figure 112008060045355-pat00015
Figure 112008060045355-pat00015

시험관에 2-(3-(벤질옥시)햅트-6-앤-1-아이닐)사이클로햅트-1-앤카바알데히드(40 mg, 0.124 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.7 mg, 0.006 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 30분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 1-(2-(벤질옥시)바이사이클로[3.1.0]핵산-1-일)-5,6,7,8-테트라하이드로-4H-사이클로햅타퓨란 14 mg (35 %)를 얻었다. Dissolve 2- (3- (benzyloxy) hapt-6-&-1-ynyl) cyclohap-1-ancarbaaldehyde (40 mg, 0.124 mmol) in toluene (1 mL) in a test tube and remove the magnetic stir bar. Put in. Then, gold (III) bromide (2.7 mg, 0.006 mmol) was added at 0 ° C, and the test tube was filled with argon, followed by sealing with a rubber septum. Then stirred at room temperature for 30 minutes. The solvent was then removed by vacuum distillation and then column chromatography to give the product 1- (2- (benzyloxy) bicyclo [3.1.0] nucleic acid-1-yl) -5,6,7,8-tetrahydro- 14 mg (35%) of 4H -cyclohaptafuran was obtained.

FT-IR(neat, cm-1) 2929, 2866, 1452, 1389, 1072, 101 1H-NMR (400MHz, CDCl3) δ 7.29~7.17 (m, 5H), 7.01 (s, 1H), 4.41 (ABq, Δδ = 58.8Hz, J = 12.4Hz, 2H), 4.30 (t, J = 8Hz, 1H), 2.55~2.46 (m, 4H), 1.96 (m, 2H), 1.82~1.73 (m, 4H), 1.60 (m, 2H), 1.46 (q, J = 6Hz, 1H), 1.32 (m, 3H), 0.95 (m, 1H) 13C-NMR (100MHz, CDCl3) δ 150.99, 138.93, 135.43, 128.26, 128.13, 127.53, 127.20, 123.83, 83.98, 71.33, 32.82, 29.81, 29.28, 28.11, 27.39, 26.05, 25.69, 24.62, 10.71 HRMS (EI) calculated for C22 H26O2322.1933 found, 322.1938.FT-IR (neat, cm -1 ) 2929, 2866, 1452, 1389, 1072, 101 1 H-NMR (400 MHz, CDCl 3 ) δ 7.29 ~ 7.17 (m, 5H), 7.01 (s, 1H), 4.41 ( ABq, Δ δ = 58.8 Hz, J = 12.4 Hz, 2H), 4.30 (t, J = 8 Hz, 1H), 2.55-2.46 (m, 4H), 1.96 (m, 2H), 1.82-1.73 (m, 4H ), 1.60 (m, 2H), 1.46 (q, J = 6 Hz, 1H), 1.32 (m, 3H), 0.95 (m, 1H) 13 C-NMR (100 MHz, CDCl 3 ) δ 150.99, 138.93, 135.43, 128.26, 128.13, 127.53, 127.20, 123.83, 83.98, 71.33, 32.82, 29.81, 29.28, 28.11, 27.39, 26.05, 25.69, 24.62, 10.71 HRMS (EI) calculated for C 22 H 26 0 2 322.1933 found, 322.1938.

실시예Example 7:  7: terttert -부틸디메틸(1-(4,5,6,7--Butyldimethyl (1- (4,5,6,7- 테트라하이드로아이소벤조퓨란Tetrahydroisobenzofuran -1-일)바이사이클로[-1-yl) bicyclo [ 3.1.0]핵산3.1.0] nucleic acid -2--2- 일옥시Iloxy )) 실란Silane

Figure 112008060045355-pat00016
Figure 112008060045355-pat00016

시험관에 2-(3-(tert-부틸디메틸실록시)햅트-6-앤-1-아이닐)사이클로핵스-1-앤카바알데히드(50 mg, 0.150 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(3.2 mg, 0.007 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 30분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 tert-부틸디메틸(1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-2-일옥시)실란 26 mg (52 %)를 얻었다.Dissolve 2- (3- (tert-butyldimethylsiloxy) hapt-6-&-1-ynyl) cyclonux-1-ancarbaaldehyde (50 mg, 0.150 mmol) in toluene (1 mL) in a test tube. A magnetic straw bar was put. Then, gold (III) bromide (3.2 mg, 0.007 mmol) was added at 0 ° C, the test tube was filled with argon, and the rubber diaphragm was blocked. Then stirred at room temperature for 30 minutes. The solvent was then removed by vacuum distillation and then column chromatography to give the product tert-butyldimethyl (1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid 26 mg (52%) of 2-yloxy) silane were obtained.

FT-IR (neat, cm-1) 2929, 2856, 1755, 1250, 1094, 1077, 1015 1H-NMR (400MHz, CDCl3) δ 7.00 (s, 1H), 4.61 (t, J = 8Hz, 1H), 2.49 (m, 4H), 2.17 (m, 1H), 1.91 (m, 1H), 1.83~1.51 (m, 5H), 1.41 (q, J = 4.4Hz, 4H), 1.26 (m, 2H), 1.41 (t, J = 4.4Hz, 1H), 0.80 (s, 9H), -0.16 (d, J = 2.8Hz, 6H) 13C-NMR (100MHz, CDCl3) δ 149.02, 134.86, 122.09, 118.38, 77.53, 30.11, 29.32, 25.74, 24.66, 23.45, 23.33, 22.90, 20.89, 20.34, 18.13, 9.38, -5.17, -5.47 HRMS (CI) calculated for C20 H33O2Si 333.2250 found, 323.2242.FT-IR (neat, cm -1 ) 2929, 2856, 1755, 1250, 1094, 1077, 1015 1 H-NMR (400 MHz, CDCl 3 ) δ 7.00 (s, 1H), 4.61 (t, J = 8 Hz, 1H ), 2.49 (m, 4H), 2.17 (m, 1H), 1.91 (m, 1H), 1.83-1.51 (m, 5H), 1.41 (q, J = 4.4 Hz, 4H), 1.26 (m, 2H) , 1.41 (t, J = 4.4 Hz, 1H), 0.80 (s, 9H), -0.16 (d, J = 2.8 Hz, 6H) 13 C-NMR (100 MHz, CDCl 3 ) δ 149.02, 134.86, 122.09, 118.38 , 77.53, 30.11, 29.32, 25.74, 24.66, 23.45, 23.33, 22.90, 20.89, 20.34, 18.13, 9.38, -5.17, -5.47 HRMS (CI) calculated for C 20 H 33 O 2 Si 333.2250 found, 323.2242.

실시예Example 8:  8: terttert -부틸(3,3-디메틸-1-(4,5,6,7--Butyl (3,3-dimethyl-1- (4,5,6,7- 테트라하이드로아이소벤조퓨란Tetrahydroisobenzofuran - 1-일)- 1 day) 바이사이클로Bicyclo [3.1.0]핵산-2-[3.1.0] nucleic acid-2- 일옥시Iloxy )) 디메틸실란Dimethylsilane

Figure 112008060045355-pat00017
Figure 112008060045355-pat00017

시험관에 2-(3-(tert-부틸디메틸실록시)-4,4-디메틸햅트-6-앤-1-아이닐)사이클로핵스-1-앤카바알데히드(50 mg, 0.138 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(3.0 mg, 0.006 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 60분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 tert-부틸(3,3-디메틸-1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-2-일옥시)디메틸실란 33 mg (65 %)를 얻었다.In vitro, 2- (3- (tert-butyldimethylsiloxy) -4,4-dimethylhapt-6-an-1-ynyl) cyclonux-1-ancarbaaldehyde (50 mg, 0.138 mmol) was added to toluene ( 1 mL) and put a magnetic stir bar. Thereafter, gold (III) bromide (3.0 mg, 0.006 mmol) was added at 0 ° C, the test tube was filled with argon, and then sealed with a rubber septum. After stirring at room temperature for 60 minutes. The solvent was then removed via vacuum distillation and then column chromatography to give the product tert-butyl (3,3-dimethyl-1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [ 3.1.0] 33 mg (65%) of nucleic acid-2-yloxy) dimethylsilane were obtained.

FT-IR (neat, cm-1) 2933, 2857, 1688, 1559, 1470, 1361, 1249, 1082, 1010; 1H-NMR (400MHz, CDCl3) δ 7.06 (s, 1H), 4.23 (s, 1H), 2.63~2.44 (m, 4H), 1.89 (m, 1H), 1.73 (m, 2H), 1.65~1.52 (m, 4H), 1.32 (t, J = 4.4Hz, 1H), 1.13 (m, 1H), 0.93 (s, 9H), 0.00 (s, 3H), -0.09 (s, 3H) 13C-NMR (100MHz, CDCl3) δ 150.21, 135.04, 122.25, 116.51, 84.49, 46.39, 43.05, 35.42, 30.65, 26.13, 25.32, 24.93, 23.81, 23.44, 21.81, 20.62, 18.39, 17.85, -4.70, -4.83 HRMS (CI) calculated for C22 H37O2Si 361.2563 found, 361.2554.FT-IR (neat, cm −1 ) 2933, 2857, 1688, 1559, 1470, 1361, 1249, 1082, 1010; 1 H-NMR (400 MHz, CDCl 3 ) δ 7.06 (s, 1H), 4.23 (s, 1H), 2.63-2.44 (m, 4H), 1.89 (m, 1H), 1.73 (m, 2H), 1.65- 1.52 (m, 4H), 1.32 (t, J = 4.4 Hz, 1H), 1.13 (m, 1H), 0.93 (s, 9H), 0.00 (s, 3H), -0.09 (s, 3H) 13 C- NMR (100 MHz, CDCl 3 ) δ 150.21, 135.04, 122.25, 116.51, 84.49, 46.39, 43.05, 35.42, 30.65, 26.13, 25.32, 24.93, 23.81, 23.44, 21.81, 20.62, 18.39, 17.85, -4.70, -4.83 HRMS (CI) calculated for C 22 H 37 0 2 Si 361.2563 found, 361.2554.

실시예Example 9:  9: 1-One- 메틸methyl -5-(4,5,6,7--5- (4,5,6,7- 테트라하이드로아이소벤조퓨란Tetrahydroisobenzofuran -1-일)-3-토실-3-아-1-yl) -3-tosyl-3-a 자바이사이클로[3.1.0]핵Java ecyclo [3.1.0] nucleus 산mountain

Figure 112008060045355-pat00018
Figure 112008060045355-pat00018

시험관에 N-(3-(2-포밀사이클로핵스-1-에닐)프로프-2-아이닐)-4-메틸-N-(2-메틸알릴)벤젠설폰아미드 (50 mg, 0.134 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.9 mg, 0.006 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 10분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 1-메틸-5-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산 40 mg (80 %)를 얻었다.In vitro add N- (3- (2-formylcyclonux-1-enyl) prop-2-ynyl) -4-methyl- N- (2-methylallyl) benzenesulfonamide (50 mg, 0.134 mmol) After dissolving in toluene (1 mL), a magnetic straw bar was added. Then, gold (III) bromide (2.9 mg, 0.006 mmol) was added at 0 ° C, and the test tube was filled with argon, followed by sealing with a rubber septum. Then stirred at room temperature for 10 minutes. The solvent was then removed via vacuum distillation and then column chromatography to give the product 1-methyl-5- (4,5,6,7-tetrahydroisobenzofuran-1-yl) -3-tosyl-3-azabi 40 mg (80%) of cyclo [3.1.0] nucleic acid were obtained.

FT-IR (neat, cm-1) 2930, 2858, 1757, 1597, 1447, 1346, 1167; 1H-NMR (400MHz, CDCl3) δ 7.68 (d, J = 8Hz, 2H), 7.33 (d, J = 7.6Hz, 2H), 6.96 (s, 1H), 3.61 (d, J = 9.2Hz, 2H), 3.27 (d, J = 8.8Hz, 1H), 2.97 (d, J = 9.2Hz, 1H), 2.44 (s, 3H), 2.40 (bs, 2H), 2.38~2.25 (m, 2H), 1.68~1.65 (m, 2H), 1.61~1.58 (m, 2H), 1.03 (ABq, Δδ = 68.0Hz, J = 4.8Hz, 2H), 0.98 (s, 3H); 13C-NMR (100MHz, CDCl3) δ 144.45, 143.45, 136.03, 133.57, 129.62, 127.54, 122.22, 119.88, 54.67, 52.44, 28.91, 28.71, 23.28, 23.00, 21.50, 20.96, 20.15, 18.61, 15.75 HRMS (EI) calculated for C21 H25NO3S 371.1555 found,371.1551.FT-IR (neat, cm −1 ) 2930, 2858, 1757, 1597, 1447, 1346, 1167; 1 H-NMR (400 MHz, CDCl 3 ) δ 7.68 (d, J = 8 Hz, 2H), 7.33 (d, J = 7.6 Hz, 2H), 6.96 (s, 1H), 3.61 (d, J = 9.2 Hz, 2H), 3.27 (d, J = 8.8 Hz, 1H), 2.97 (d, J = 9.2 Hz, 1H), 2.44 (s, 3H), 2.40 (bs, 2H), 2.38-2.25 (m, 2H), 1.68-1.65 (m, 2H), 1.61-1.58 (m, 2H), 1.03 (ABq, Δ δ = 68.0 Hz, J = 4.8 Hz, 2H), 0.98 (s, 3H); 13 C-NMR (100 MHz, CDCl 3 ) δ 144.45, 143.45, 136.03, 133.57, 129.62, 127.54, 122.22, 119.88, 54.67, 52.44, 28.91, 28.71, 23.28, 23.00, 21.50, 20.96, 20.15, 18.61, 15.75 HRMS (EI) calculated for C 21 H 25 NO 3 S 371.1555 found, 371.1551.

실시예Example 10:  10: 1-One- 메틸methyl -5-(5,6,7,8--5- (5,6,7,8- 테트라하이드로Tetrahydro -4H--4H- 사이클로햅타[Cyclohapta [ cc ]퓨란Furan -1-일)-3-토실-3--1-yl) -3-tosyl-3- 아자바이사이클로[3.1.0]핵산Azabicyclo [3.1.0] Nucleic Acid

Figure 112008060045355-pat00019
Figure 112008060045355-pat00019

시험관에 N-(3-(2-포밀사이클로햅트-1-에닐)프로프-2-아이닐)-4-메틸-N-(2-메틸알릴)벤젠설폰아미드 (50 mg, 0.129 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.8 mg, 0.006 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 10분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 1-메틸-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산 44 mg (88 %)를 얻었다.In vitro add N- (3- (2-formylcyclohap-1-enyl) prop-2-ynyl) -4-methyl- N- (2-methylallyl) benzenesulfonamide (50 mg, 0.129 mmol) After dissolving in toluene (1 mL), a magnetic straw bar was added. Thereafter, gold (III) bromide (2.8 mg, 0.006 mmol) was added at 0 ° C, the test tube was filled with argon, and the rubber diaphragm was blocked. Then stirred at room temperature for 10 minutes. The solvent was then removed by vacuum distillation and then column chromatography to give the product 1-methyl-5- (5,6,7,8-tetrahydro-4 H -cyclohapta [ c ] furan-1-yl) -3 44 mg (88%) of tosyl-3-azabicyclo [3.1.0] nucleic acid were obtained.

FT-IR (neat, cm-1) 2928, 2857, 1758, 1597, 1446, 1345, 1164 1H-NMR (400MHz, CDCl3) δ 7.67 (d, J=8Hz, 2H), 7.32 (d, J = 8.4Hz, 2H), 6.94 (s, 1H), 3.62 (d, J = 9.2Hz, 2H), 3.06 (ABq, Δδ = 44.0Hz, J = 9.2Hz, 2H), 2.44 (s, 3H), 2.42~2.39 (m, 2H), 2.35~2.31 (m, 2H), 1.78~1.69 (m, 2H), 1.57~1.45 (m, 2H), 0.99 (ABq, Δδ = 112.0Hz, J = 4.4Hz), 0.98 (s, 3H); 13C-NMR (100MHz, CDCl3) δ 145.90, 143.45, 136.62, 133.53, 129.60, 128.21, 127.53, 126.15, 54.72, 53.85, 32.68, 29.59, 28.48, 28.45, 27.95, 25.85, 25.70, 21.52, 19.35, 16.05 HRMS (EI) calculated for C22 H27NO3S 385.1712 found, 385.1717.FT-IR (neat, cm -1 ) 2928, 2857, 1758, 1597, 1446, 1345, 1164 1 H-NMR (400 MHz, CDCl 3 ) δ 7.67 (d, J = 8 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.94 (s, 1H), 3.62 (d, J = 9.2 Hz, 2H), 3.06 (ABq, Δ δ = 44.0 Hz, J = 9.2 Hz, 2H), 2.44 (s, 3H) , 2.42 to 2.39 (m, 2H), 2.35 to 2.31 (m, 2H), 1.78 to 1.69 (m, 2H), 1.57 to 1.45 (m, 2H), 0.99 (ABq, Δ δ = 112.0 Hz, J = 4.4 Hz), 0.98 (s, 3 H); 13 C-NMR (100 MHz, CDCl 3 ) δ 145.90, 143.45, 136.62, 133.53, 129.60, 128.21, 127.53, 126.15, 54.72, 53.85, 32.68, 29.59, 28.48, 28.45, 27.95, 25.85, 25.70, 21.52, 19.35, 19.05 HRMS (EI) calculated for C 22 H 27 NO 3 S 385.1712 found, 385.1717.

실시예 11: 1- 페닐 -5-(4,5,6,7- 테트라하이드로아이소벤조퓨란 -1-일)-3- 토실 -3-아 자바이사이클로[3.1.0]핵 산 Example 11: 1- phenyl -5- (4,5,6,7 -tetrahydroisobenzofuran -1-yl) -3- tosyl- 3-a jabacyclo [3.1.0] nucleic acid

Figure 112008060045355-pat00020
Figure 112008060045355-pat00020

시험관에 N-(3-(2-포밀사이클로핵스-1-에닐)프로프-2-아이닐)-4-메틸-N-(2-페닐알릴)벤젠설폰아미드 (50 mg, 0.115 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.5 mg, 0.005 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 60분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 1-페닐-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산 31 mg (62 %)를 얻었다.In vitro, N- (3- (2-formylcyclonux-1-enyl) prop-2-ynyl) -4-methyl- N- (2-phenylallyl) benzenesulfonamide (50 mg, 0.115 mmol) was added to the test tube. After dissolving in toluene (1 mL), a magnetic straw bar was added. Thereafter, gold (III) bromide (2.5 mg, 0.005 mmol) was added at 0 ° C, the test tube was filled with argon, and the rubber diaphragm was blocked. After stirring at room temperature for 60 minutes. The solvent is then removed via vacuum distillation followed by column chromatography the product 1-phenyl-5- (5,6,7,8-tetrahydro- 4H -cyclohaptafuran-1-yl) -3-tosyl- 31 mg (62%) of 3-azabicyclo [3.1.0] nucleic acid were obtained.

FT-IR (neat, cm-1) 2930, 2856, 1598, 1446, 1348, 1164, 1104, 1015 1H-NMR (400MHz, CDCl3) δ 7.72 (d, J = 8.4Hz, 2H), 7.35 (d, J = 8.0Hz, 2H), 7.18~7.12 (m, 3H), 6.98~6.96 (m, 2H), 6.89 (s, 1H), 3.82 (ABq, Δδ = 52.0Hz, J = 9.2Hz, 2H), 3.47 (ABq, Δδ = 40.0Hz, J = 9.2Hz, 2H), 2.46 (s, 3H), 2.38~2.28 (m, 4H), 2.18~2.14 (m, 1H), 1.66 (d, J = 5.2Hz, 1H), 1.61~1.55 (m, 2H), 1.47 (bs, 2H); 13C-NMR (100MHz, CDCl3) δ 143.65, 142.76, 137.26, 136.12, 133.41, 129.73, 128.08, 127.60, 126.72, 122.24, 120.04, 54.75, 52.58, 36.85, 31.64, 23.13, 22.83, 21.57, 20.98, 20.08, 18.39 HRMS (EI) calculated for C26 H27NO3S 433.1711 found, 433.1709.FT-IR (neat, cm -1 ) 2930, 2856, 1598, 1446, 1348, 1164, 1104, 1015 1 H-NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 8.4 Hz, 2H), 7.35 ( d, J = 8.0 Hz, 2H), 7.18-7.72 (m, 3H), 6.98-6.96 (m, 2H), 6.89 (s, 1H), 3.82 (ABq, Δ δ = 52.0 Hz, J = 9.2 Hz, 2H), 3.47 (ABq, Δ δ = 40.0 Hz, J = 9.2 Hz, 2H), 2.46 (s, 3H), 2.38-2.28 (m, 4H), 2.18-2.14 (m, 1H), 1.66 (d, J = 5.2 Hz, 1H), 1.61-1.55 (m, 2H), 1.47 (bs, 2H); 13 C-NMR (100 MHz, CDCl 3 ) δ 143.65, 142.76, 137.26, 136.12, 133.41, 129.73, 128.08, 127.60, 126.72, 122.24, 120.04, 54.75, 52.58, 36.85, 31.64, 23.13, 22.83, 21.57, 20.98, 20.98 , 18.39 HRMS (EI) calculated for C 26 H 27 NO 3 S 433.1711 found, 433.1709.

실시예Example 12:  12: 1-One- 페닐Phenyl -5-(5,6,7,8--5- (5,6,7,8- 테트라하이드로Tetrahydro -4-4 HH -- 사이클로햅타[Cyclohapta [ cc ]퓨란Furan -1-일)-3-토실-3--1-yl) -3-tosyl-3- 아자바이사이클로[3.1.0]핵산Azabicyclo [3.1.0] Nucleic Acid

Figure 112008060045355-pat00021
Figure 112008060045355-pat00021

시험관에 N-(3-(2-포밀사이클로햅트-1-에닐)프로프-2-아이닐)-4-메틸-N-(2-페닐알릴)벤젠설폰아미드 (50 mg, 0.111 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.4 mg, 0.005 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 30분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그 래피를 통해 생성물 1-페닐-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산 45 mg (90 %)를 얻었다.In vitro add N- (3- (2-formylcyclohap-1-enyl) prop-2-ynyl) -4-methyl- N- (2-phenylallyl) benzenesulfonamide (50 mg, 0.111 mmol) After dissolving in toluene (1 mL), a magnetic straw bar was added. Then, gold (III) bromide (2.4 mg, 0.005 mmol) was added at 0 ° C, and the test tube was filled with argon, followed by sealing with a rubber septum. Then stirred at room temperature for 30 minutes. The solvent was then removed by vacuum distillation and then the product was purified by column chromatography to give the product 1-phenyl-5- (5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan-1-yl)- 45 mg (90%) of 3-tosyl-3-azabicyclo [3.1.0] nucleic acid were obtained.

FT-IR (neat, cm-1) 2922, 2848, 1763, 1598, 1447, 1348, 1166, 1104, 1028 1H-NMR (400MHz, CDCl3) δ 7.72 (d, J = 8.0Hz, 2H), 7.35 (d, J = 8.0Hz, 2H), 7.16~7.11 (m, 3H), 6.91~6.89 (m, 3H), 3.83 (ABq, Δδ = 56.0Hz, J = 9.2Hz, 2H), 3.57 (d, J = 9.2Hz, 1H), 3.33 (d, J = 9.6Hz, 1H), 2.45 (s, 3H), 2.36 (d, J = 6.4Hz, 1H), 2.30 (d, J = 9.6Hz, 1H), 2.23~2.21 (m, 2H), 1.63 (dd, J = 5.6Hz, 4H), 1.41~1.38 (m, 3H), 1.10 (d, J = 6Hz, 1H); 13C-NMR (100MHz, CDCl3) δ 143.89, 143.67, 137.13, 136.69, 133.32, 129.69, 128.29, 127.97, 127.58, 127.12, 126.49, 53.90, 53.79, 35.86, 32.50, 31.65, 29.50, 28.84, 25.74, 25.61, 21.51, 19.73; HRMS (EI) calculated for C27 H29NO3S 447.1868 found, 447.1870.FT-IR (neat, cm -1 ) 2922, 2848, 1763, 1598, 1447, 1348, 1166, 1104, 1028 1 H-NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.16-7.11 (m, 3H), 6.91-6.89 (m, 3H), 3.83 (ABq, Δ δ = 56.0 Hz, J = 9.2 Hz, 2H), 3.57 ( d, J = 9.2 Hz, 1H), 3.33 (d, J = 9.6 Hz, 1H), 2.45 (s, 3H), 2.36 (d, J = 6.4 Hz, 1H), 2.30 (d, J = 9.6 Hz, 1H), 2.23-2.21 (m, 2H), 1.63 (dd, J = 5.6 Hz, 4H), 1.41-1.38 (m, 3H), 1.10 (d, J = 6 Hz, 1H); 13 C-NMR (100 MHz, CDCl 3 ) δ 143.89, 143.67, 137.13, 136.69, 133.32, 129.69, 128.29, 127.97, 127.58, 127.12, 126.49, 53.90, 53.79, 35.86, 32.50, 31.65, 29.50, 28.84, 25.84, 25.84. , 21.51, 19.73; HRMS (EI) calculated for C 27 H 29 NO 3 S 447.1868 found, 447.1870.

실시예Example 13:  13: 3,6-3,6- 디페닐Diphenyl -1-(4,5,6,7--1- (4,5,6,7- 테트라하이드로아이소벤조퓨란Tetrahydroisobenzofuran -1-일)-3--1-yl) -3- 아자바이사이클로[3.1.0]핵산Azabicyclo [3.1.0] Nucleic Acid

Figure 112008060045355-pat00022
Figure 112008060045355-pat00022

시험관에 (Z)-2-(3-(페닐알릴)아미노)프로프-1-아이닐)사이클로핵스-1-엔카 바알데히드 (40 mg, 0.112 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.4 mg, 0.005 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 30분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 3,6-디페닐-1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)-3-아자바이사이클로[3.1.0]핵산 22mg (55 %)를 얻었다.Dissolve (Z) -2- (3- (phenylallyl) amino) prop-1-ynyl) cyclonux-1-eneka Baaldehyde (40 mg, 0.112 mmol) in toluene (1 mL) in a test tube I put a stick. Then, gold (III) bromide (2.4 mg, 0.005 mmol) was added at 0 ° C, and the test tube was filled with argon, followed by sealing with a rubber septum. Then stirred at room temperature for 30 minutes. The solvent was then removed by vacuum distillation and then column chromatography to give the product 3,6-diphenyl-1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) -3-azabicyclo [3.1.0] 22 mg (55%) of nucleic acid were obtained.

FT-IR (neat, cm-1) 2929, 2850, 1598, 1504, 1476, 1364, 1199, 1119 1H-NMR (400MHz, CDCl3) δ 7.22 (d, J = 87.6Hz, 2H), 7.14~7.08 (m, 2H), 6.94 (s, 1H), 6.84 (d, J = 6.8Hz, 2H), 6.72 (t, J = 7.2Hz, 1H), 6.62 (d, J = 8.0Hz, 2H), 3.92 (ABq, Δδ = 68.0Hz, J = 9.2Hz, 1H), 3.56 (dd, J = 4.0, 4.4Hz, 1H), 3.36 (d, J = 9.2Hz, 1H), 2.54 (t, J = 4.0Hz, 1H), 2.41 (d, J = 4.8Hz, 3H), 2.36~2.29 (m, 1H), 2.33 (ddd, J = 14.0, 3.6, 6.4Hz, 1H), 1.57 (m, 2H), 1.43~1.39 (m, 1H), 1.25 (bs, 1H); 13C-NMR (100MHz, CDCl3) δ 147.98, 144.26. 138.29, 135.71, 129.23, 127.66, 127.03, 125.64, 122.11, 120.38, 116.68, 112.31, 55.01, 50.58, 33.64, 33.46, 29.39, 23.13, 23.10, 20.47, 20.14; HRMS (EI) calculated for C25H25NO 355.1936 found,355.1930.FT-IR (neat, cm -1 ) 2929, 2850, 1598, 1504, 1476, 1364, 1199, 1119 1 H-NMR (400 MHz, CDCl 3 ) δ 7.22 (d, J = 87.6 Hz, 2H), 7.14- 7.08 (m, 2H), 6.94 (s, 1H), 6.84 (d, J = 6.8 Hz, 2H), 6.72 (t, J = 7.2 Hz, 1H), 6.62 (d, J = 8.0 Hz, 2H), 3.92 (ABq, Δ δ = 68.0 Hz, J = 9.2 Hz, 1H ), 3.56 (dd, J = 4.0, 4.4 Hz, 1H), 3.36 (d, J = 9.2 Hz, 1H), 2.54 (t, J = 4.0 Hz, 1H), 2.41 (d, J = 4.8 Hz, 3H), 2.36-2.29 (m, 1H), 2.33 (ddd, J = 14.0, 3.6, 6.4 Hz, 1H), 1.57 (m, 2H), 1.43-1.39 (m, 1 H), 1.25 (bs, 1 H); 13 C-NMR (100 MHz, CDCl 3 ) δ 147.98, 144.26. 138.29, 135.71, 129.23, 127.66, 127.03, 125.64, 122.11, 120.38, 116.68, 112.31, 55.01, 50.58, 33.64, 33.46, 29.39, 23.13, 23.10, 20.47, 20.14; HRMS (EI) calculated for C 25 H 25 NO 355.1936 found, 355.1930.

실시예Example 14:  14: 3,6-3,6- 디페닐Diphenyl -1-(5,6,7,8--1- (5,6,7,8- 테트라하이드로Tetrahydro -4-4 HH -- 사이클로햅타[Cyclohapta [ cc ]퓨란Furan -1-일)-3--1-yl) -3- 아자바이사이클로[3.1.0]핵산Azabicyclo [3.1.0] Nucleic Acid

Figure 112008060045355-pat00023
Figure 112008060045355-pat00023

시험관에 (Z)-2-(3-(페닐(3-페닐알릴)아미노)프로프-1-아이닐)사이클로햅트-1-엔카바알데히드 (40 mg, 0.108 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.3 mg, 0.005 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 25분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 3,6-디페닐-1-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)-3-아자바이사이클로[3.1.0]핵산 23mg (58 %)를 얻었다.In vitro, (Z) -2- (3- (phenyl (3-phenylallyl) amino) prop-1-ynyl) cyclohap-1-enecaraldehyde (40 mg, 0.108 mmol) was added to toluene (1 mL). After thawing in, put a magnetic straw bar. Thereafter, gold (III) bromide (2.3 mg, 0.005 mmol) was added at 0 ° C, the test tube was filled with argon, and the rubber diaphragm was blocked. Then stirred at room temperature for 25 minutes. The solvent is then removed via vacuum distillation followed by column chromatography to give the product 3,6-diphenyl-1- (5,6,7,8-tetrahydro-4 H -cyclohapta [ c ] furan-1-yl 23 mg (58%) of azabicyclo [3.1.0] nucleic acid were obtained.

FT-IR (neat, cm-1) 2921, 2843, 1674, 1599, 1505, 1477, 1365, 1199, 1123, 1031, 994 1H-NMR (400MHz, CDCl3) δ 7.25~7.21 (m, 2H), 7.13~7.06 (m, 2H), 6.95 (s, 1H), 6.76~6.70 (m, 3H), 6.61 (d, J = 8.0 Hz, 2H), 3.88 (ABq, Δδ = 40.0Hz, J = 9.2 Hz, 1H), 3.58 (dd, J = 4.0, 4.0Hz, 1H), 3.36 (d, J = 9.2Hz, 1H), 2.51 (t, J = 4.4 Hz, 1H), 2.38 (d, J = 4.4 Hz, 2H), 2.31~2.19 (m, 3H), 1.67~1.57 (m, 2H), 1.47~1.42 (m, 42H), 1.36~1.19 (m, 2H) 13C-NMR (100MHz, CDCl3) δ 147.95, 145.02. 138.45, 136.14, 129.20, 128.30, 127.61, 126.76, 126.39, 125.58, 116.67, 112.30, 55.66, 50.62, 33.60, 33.50, 32.54, 29.89, 29.71, 28.56, 25.94, 25.64 HRMS (EI) calculated for C25H25NO 369.2093 found, 369.2098.FT-IR (neat, cm -1 ) 2921, 2843, 1674, 1599, 1505, 1477, 1365, 1199, 1123, 1031, 994 1 H-NMR (400MHz, CDCl 3 ) δ 7.25 ~ 7.21 (m, 2H), 7.13 ~ 7.06 (m, 2H), 6.95 (s, 1H), 6.76 ~ 6.70 (m, 3H), 6.61 (d, J = 8.0 Hz, 2H), 3.88 (ABq, Δ δ = 40.0 Hz, J = 9.2 Hz, 1H), 3.58 (dd, J = 4.0, 4.0 Hz, 1H), 3.36 (d, J = 9.2 Hz, 1H) , 2.51 (t, J = 4.4 Hz, 1H), 2.38 (d, J = 4.4 Hz, 2H), 2.31-2.19 (m, 3H), 1.67-1.57 (m, 2H), 1.47-1.42 (m, 42H ), 1.36-1.19 (m, 2H) 13 C-NMR (100 MHz, CDCl 3 ) δ 147.95, 145.02. 138.45, 136.14, 129.20, 128.30, 127.61, 126.76, 126.39, 125.58, 116.67, 112.30, 55.66, 50.62, 33.60, 33.50, 32.54, 29.89, 29.71, 28.56, 25.94, 25.64 HRMS (EI) calculated for C 25 H 25 NO 369.2093 found, 369.2098.

실시예Example 15:  15: 디에틸Diethyl -1-(4,5,6,7--1- (4,5,6,7- 테트라하이드로아이소벤조퓨란Tetrahydroisobenzofuran -1-일)-1 day) 바이사이클로Bicyclo [[ 3.1.0]핵산3.1.0] nucleic acid -3,3-디카복실-3,3-dicarboxyl 에이트Eight

Figure 112008060045355-pat00024
Figure 112008060045355-pat00024

시험관에 디에틸 2-알릴-2-(3-(2-포밀사이클로핵스-1-에닐)프로프-2-아이닐)말로네이트 (50 mg, 0.144 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(3.1 mg, 0.007 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 10분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 디에틸-1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실에이트 5mg (10 %)를 얻었다.Diethyl 2-allyl-2- (3- (2-formylcyclonux-1-enyl) prop-2-ynyl) malonate (50 mg, 0.144 mmol) was dissolved in toluene (1 mL) in a test tube. A magnetic straw bar was put. Then, gold (III) bromide (3.1 mg, 0.007 mmol) was added at 0 ° C, the test tube was filled with argon, and the rubber diaphragm was blocked. Then stirred at room temperature for 10 minutes. The solvent is then removed via vacuum distillation and then the product diethyl-1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid-3 via column chromatography 5 mg (10%) of 3-dicarboxylate was obtained.

FT-IR (neat, cm-1) 2981, 2933, 2857, 1732, 1444, 1368, 1244, 1181, 1154, 1095 1H-NMR (400MHz, CDCl3) δ 6.96 (s, 1H), 4.22~4.12 (m, 4H), 2.86 (d, J = 13.6 Hz, 1H), 2.71 (d, J = 13.6Hz, 1H), 2.65~2.60 (m, 2H), 2.55~2.52 (m, 2H), 2.50~2.47 (m, 2H), 1.73~1.60 (m, 5H), 1.27~1.20 (m, 6H), 0.98~0.94 (m, 1H), 0.60~0.57 (m, 1H); 13C-NMR (100 MHz, CDCl3) δ 172.71, 171.61, 149.03, 134.59, 122.39, 116.42, 94.36, 61.74, 61.61, 59.63, 39.10, 35.78, 26.22, 24.45, 23.44, 23.12, 20.99, 20.33, 15.67, 13.97 HRMS (EI) calculated for C20 H26O5 346.1780 found, 346.1782.FT-IR (neat, cm -1 ) 2981, 2933, 2857, 1732, 1444, 1368, 1244, 1181, 1154, 1095 1 H-NMR (400MHz, CDCl 3 ) δ 6.96 (s, 1H), 4.22 ~ 4.12 (m, 4H), 2.86 ( d, J = 13.6 Hz, 1H), 2.71 (d, J = 13.6Hz, 1H), 2.65 ~ 2.60 (m, 2H), 2.55 ~ 2.52 (m, 2H), 2.50 ~ 2.47 (m, 2H), 1.73-1.60 (m, 5H), 1.27-1.20 (m, 6H), 0.98-0.94 (m, 1H), 0.60-0.57 (m, 1H); 13 C-NMR (100 MHz, CDCl 3 ) δ 172.71, 171.61, 149.03, 134.59, 122.39, 116.42, 94.36, 61.74, 61.61, 59.63, 39.10, 35.78, 26.22, 24.45, 23.44, 23.12, 20.99, 20.33, 15.67, 13.97 HRMS (EI) calculated for C 20 H 26 0 5 346.1780 found, 346.1782.

실시예Example 16:  16: 디에틸Diethyl -1-(5,6,7,8--1- (5,6,7,8- 테트라하이드로Tetrahydro -4-4 HH -- 사이클로햅타[Cyclohapta [ cc ]퓨란Furan -1-일)-1 day) 바이사이클로Bicyclo [3.1.0]핵산-3,3-[3.1.0] nucleic acid-3,3- 디카복실에이트Dicarboxylate

Figure 112008060045355-pat00025
Figure 112008060045355-pat00025

시험관에 디에틸 2-알릴-2-(3-(2-포밀사이클로햅트-1-에닐)프로프-2-아이닐)말로네이트 (50 mg, 0.138 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(3.0 mg, 0.007 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 25분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 디에틸-1-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실에이트 20mg (40 %)를 얻었다.Diethyl 2-allyl-2- (3- (2-formylcyclohap-1-enyl) prop-2-ynyl) malonate (50 mg, 0.138 mmol) was dissolved in toluene (1 mL) in a test tube. A magnetic straw bar was put. Then, gold (III) bromide (3.0 mg, 0.007 mmol) was added at 0 ° C, the test tube was filled with argon, and the rubber diaphragm was blocked. Then stirred at room temperature for 25 minutes. The solvent was then removed via vacuum distillation followed by column chromatography the product diethyl-1- (5,6,7,8-tetrahydro-4 H -cyclohapta [ c ] furan-1-yl) bicyclo [ 3.1.0] 20 mg (40%) of nucleic acid-3,3-dicarboxylate were obtained.

FT-IR (neat, cm-1) 2980, 2921, 2846, 1732, 1446, 1366, 1245 1H-NMR (400MHz, CDCl3) δ 6.94 (s, 1H), 4.23~4.12 (m, 4H), 2.85 (d, J = 13.6Hz, 1H), 2.66~2.42 (m, 7H), 1.76 (bs, 2H), 1.68~1.63 (m, 5H), 1.28~1.20 (m, 6H), 0.90~0.86 (m, 1H), 0.63~0.60 (m, 1H) 13C-NMR (100MHz, CDCl3) δ 172.73, 171.56, 150.43, 135.28, 128.32, 123.26, 61.72, 61.63, 59.77, 40.63, 35.79, 32.78, 29.69, 29.42, 25.95, 25.61, 25.27, 24.19, 15.13, 13.98; HRMS (EI) calculated for C21 H28O5 360.1937 found, 360.1934.FT-IR (neat, cm -1 ) 2980, 2921, 2846, 1732, 1446, 1366, 1245 1 H-NMR (400MHz, CDCl 3 ) δ 6.94 (s, 1H), 4.23 ~ 4.12 (m, 4H), 2.85 (d, J = 13.6Hz, 1H), 2.66 ~ 2.42 (m, 7H), 1.76 ( bs, 2H), 1.68-1.63 (m, 5H), 1.28-1.20 (m, 6H), 0.90-0.86 (m, 1H), 0.63-0.60 (m, 1H) 13 C-NMR (100 MHz, CDCl 3 ) δ 172.73, 171.56, 150.43, 135.28, 128.32, 123.26, 61.72, 61.63, 59.77, 40.63, 35.79, 32.78, 29.69, 29.42, 25.95, 25.61, 25.27, 24.19, 15.13, 13.98; HRMS (EI) calculated for C 21 H 28 O 5 360.1937 found, 360.1934.

실시예Example 17:  17: 디에틸Diethyl -1-(4,5,6,7,8,9--1- (4,5,6,7,8,9- 핵사하이드로사이클로옥타[Nucleus hydrocycloocta [ cc ]퓨란Furan -1-일)바이사이클로[-1-yl) bicyclo [ 3.1.0]핵산3.1.0] nucleic acid -3,3--3,3- 디카복실에이트Dicarboxylate

Figure 112008060045355-pat00026
Figure 112008060045355-pat00026

시험관에 (Z)-디에틸 2-알릴-2-(3-(2-포밀사이클로옥트-1-에닐)프로프-2-아이닐)말로네이트 (50 mg, 0.133 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.9 mg, 0.006 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 10분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 디에틸-1-(4,5,6,7,8,9-핵사하이드로사이클로옥타[c]퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실에이트 22mg (45 %)를 얻었다.To the test tube was added (Z) -diethyl 2-allyl-2- (3- (2-formylcyclooct-1-enyl) prop-2-ynyl) malonate (50 mg, 0.133 mmol) toluene (1 mL). ), And then put a magnetic stir bar. Then, gold (III) bromide (2.9 mg, 0.006 mmol) was added at 0 ° C, and the test tube was filled with argon, followed by sealing with a rubber septum. Then stirred at room temperature for 10 minutes. The solvent is then removed by vacuum distillation and then the product diethyl-1- (4,5,6,7,8,9-nuxahydrocycloocta [ c ] furan-1-yl) bicyclo [ 3.1.0] 22 mg (45%) of nucleic acid-3,3-dicarboxylate were obtained.

FT-IR (neat, cm-1) 2979, 2930, 2856, 1731, 1445, 1366, 1249, 1180, 1094, 1068, 1012; 1H-NMR (400MHz, CDCl3) δ 6.96 (s, 1H), 4.23~4.12 (m, 4H), 2.86 (d, J = 13.6Hz, 1H), 2.66~2.42 (m, 7H), 1.76 (bs, 2H), 1.68~1.63 (m, 5H), 1.26 (t, J = 7.6Hz, 6H), 0.90~0.86 (m, 1H), 0.63~0.60 (m, 1H); 13C-NMR (100MHz, CDCl3) δ 172.72, 171.61, 150.61, 135.60, 126.83, 120.81, 61.74, 61.61, 59.74, 40.38, 35.81, 31.69, 30.39, 25.64, 25.59, 24.23, 22.28, 21.30, 15.67, 13.97 HRMS (EI) calculated for C22 H30O5 374.2093; found, 374.2098.FT-IR (neat, cm −1 ) 2979, 2930, 2856, 1731, 1445, 1366, 1249, 1180, 1094, 1068, 1012; 1 H-NMR (400 MHz, CDCl 3 ) δ 6.96 (s, 1H), 4.23 ~ 4.12 (m, 4H), 2.86 (d, J = 13.6Hz, 1H), 2.66 ~ 2.42 (m, 7H), 1.76 ( bs, 2H), 1.68-1.63 (m, 5H), 1.26 (t, J = 7.6 Hz, 6H), 0.90-0.86 (m, 1H), 0.63-0.60 (m, 1H); 13 C-NMR (100 MHz, CDCl 3 ) δ 172.72, 171.61, 150.61, 135.60, 126.83, 120.81, 61.74, 61.61, 59.74, 40.38, 35.81, 31.69, 30.39, 25.64, 25.59, 24.23, 22.28, 21.30, 15.67, 13.97 HRMS (EI) calculated for C 22 H 30 O 5 374.2093; found, 374.2098.

실시예Example 18:  18: 디에틸Diethyl -1--One- 페닐Phenyl -5-(4,5,6,7--5- (4,5,6,7- 테트라하이드로아이소벤조퓨란Tetrahydroisobenzofuran -1-일)바이사이클로[-1-yl) bicyclo [ 3.1.0]핵산3.1.0] nucleic acid -3,3--3,3- 디카복실에이트Dicarboxylate

Figure 112008060045355-pat00027
Figure 112008060045355-pat00027

시험관에 디에틸 2-(3-(2-포밀사이클로핵스-1-에닐)프로프-2-아이닐)-2-(2-페닐알릴)말로네이트 (40 mg, 0.094 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.1 mg, 0.004 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 0℃에서 15분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 디에틸-1-페닐-5-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실에이트 15mg (37 %)를 얻었다.Diethyl 2- (3- (2-formylcyclonux-1-enyl) prop-2-ynyl) -2- (2-phenylallyl) malonate (40 mg, 0.094 mmol) was added to the test tube in toluene (1). mL) and put a magnetic stir bar. Thereafter, gold (III) bromide (2.1 mg, 0.004 mmol) was added at 0 ° C, the test tube was filled with argon, and then sealed with a rubber septum. Then, it stirred at 0 degreeC for 15 minutes. The solvent was then removed via vacuum distillation followed by column chromatography the product diethyl-1-phenyl-5- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0 ] 15 mg (37%) of nucleic acid-3,3-dicarboxylate were obtained.

FT-IR (neat, cm-1) 2930, 2855, 1730, 1445, 1246, 1182, 1094; 1H-NMR (400MHz, CDCl3) δ 7.18~7.08 (m, 5H), 6.90 (s, 1H), 4.27~4.16 (m, 4H), 3.09~2.89 (m, 1H), 2.39~2.34 (m, 2H), 2.27~2.24 (m, 2H), 1.64~1.57 (m, 2H), 1.46 (d, J = 5.2Hz, 2H), 1.30~1.22 (m, 7H), 1.13 (d, J = 5.6Hz, 1H); 13C-NMR (100MHz, CDCl3) δ 172.72, 171.63, 145.81, 140.72,135.29,128.03, 127.81, 125.98, 122.15, 118.59, 61.87, 61.74, 57.89, 42.44, 40.05, 38.54, 33.36, 29.68, 23.32, 22.97, 21.22, 20.23, 19.73, 13.99 HRMS (EI) calculated for C26 H30O5 422.2093; found, 422.2090.FT-IR (neat, cm −1 ) 2930, 2855, 1730, 1445, 1246, 1182, 1094; 1 H-NMR (400 MHz, CDCl 3 ) δ 7.18 to 7.08 (m, 5H), 6.90 (s, 1H), 4.27 ~ 4.16 (m, 4H), 3.09 ~ 2.89 (m, 1H), 2.39 ~ 2.34 (m, 2H), 2.27 ~ 2.24 (m, 2H), 1.64 ~ 1.57 (m, 2H), 1.46 (d, J = 5.2 Hz, 2H), 1.30-1.22 (m, 7H), 1.13 (d, J = 5.6 Hz, 1H); 13 C-NMR (100 MHz, CDCl 3 ) δ 172.72, 171.63, 145.81, 140.72,135.29,128.03, 127.81, 125.98, 122.15, 118.59, 61.87, 61.74, 57.89, 42.44, 40.05, 38.54, 33.36, 29.68, 23.32, 22.32, 22. , 21.22, 20.23, 19.73, 13.99 HRMS (EI) calculated for C 26 H 30 O 5 422.2093; found, 422.2090.

실시예Example 19:  19: 디에틸Diethyl 1- One- 페닐Phenyl -5-(5,6,7,8--5- (5,6,7,8- 테트라하이드로Tetrahydro -4-4 HH -- 사이클로햅타[Cyclohapta [ cc ]퓨란Furan -1-일)-1 day) 바이사이클로Bicyclo [3.1.0]핵산-3,3-[3.1.0] nucleic acid-3,3- 디카복실에이트Dicarboxylate

Figure 112008060045355-pat00028
Figure 112008060045355-pat00028

시험관에 디에틸 2-알릴-2-(3-(2-포밀사이클로햅트-1-에닐)프로프-2-아이닐)-2-(2-페닐알릴)말로네이트(40 mg, 0.091 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.0 mg, 0.004 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 0℃에서 10분간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그 래피를 통해 생성물 디에틸-1-페닐-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실에이트 22mg (55 %)를 얻었다.Diethyl 2-allyl-2- (3- (2-formylcyclohap-1-enyl) prop-2-ynyl) -2- (2-phenylallyl) malonate (40 mg, 0.091 mmol) in vitro Was dissolved in toluene (1 mL), and a magnetic spoon was added thereto. Then, gold (III) bromide (2.0 mg, 0.004 mmol) was added at 0 ° C, and the test tube was filled with argon, followed by sealing with a rubber septum. Then, it stirred at 0 degreeC for 10 minutes. The solvent is then removed via vacuum distillation and then the product diethyl-1-phenyl-5- (5,6,7,8-tetrahydro-4 H -cyclohapta [ c ] furan-1- via column chromatography Il) Bicyclo [3.1.0] nucleic acid-3,3-dicarboxylate 22 mg (55%) were obtained.

FT-IR (neat, cm-1) 2981, 2930, 2855, 1833, 1733, 1447, 1250, 1094; 1H-NMR (400MHz, CDCl3) δ 7.14~7.06 (m, 3H), 7.00 (d, J = 7.2Hz, 2H), 6.92 (s, 1H), 4.28~4.17 (m, 4H), 3.02~2.96 (m, 2H), 2.98 (ABq, Δδ = 124.0Hz, J = 14.0 Hz, 2H), 2.43~2.37 (m, 1H), 2.31~2.25 (m, 3H), 1.73~1.65 (m, 1H), 1.60~1.49 (m, 3H), 1.44~1.33 (m, 2H), 1.30~1.22 (m, 6H), 1.19 (d, J = 6.0Hz, 1H), 0.98~0.88 (m, 1H); 13C-NMR (100MHz, CDCl3) δ 172.63, 171.66, 147.12, 140.39, 135.88,128.31, 127.68, 126.99, 125.74, 125.00, 61.88, 61.76, 57.78, 41.89, 40.00, 37.38, 33.56, 32.61, 29.66, 28.78, 25.91, 25.72, 20.93, 13.98 HRMS (EI) calculated for C27H32O5 436.2250 found,436.2242.FT-IR (neat, cm −1 ) 2981, 2930, 2855, 1833, 1733, 1447, 1250, 1094; 1 H-NMR (400 MHz, CDCl 3 ) δ 7.14 to 7.06 (m, 3H), 7.00 (d, J = 7.2 Hz, 2H), 6.92 (s, 1H), 4.28 to 4.17 (m, 4H), 3.02 to 2.96 (m, 2H), 2.98 (ABq, Δ δ = 124.0 Hz, J = 14.0 Hz, 2H), 2.43-2.37 (m, 1H), 2.31-2.25 (m, 3H), 1.73-1.65 (m, 1H ), 1.60-1.49 (m, 3H), 1.44-1.33 (m, 2H), 1.30-1.22 (m, 6H), 1.19 (d, J = 6.0 Hz, 1H), 0.98-0.88 (m, 1H); 13 C-NMR (100 MHz, CDCl 3 ) δ 172.63, 171.66, 147.12, 140.39, 135.88,128.31, 127.68, 126.99, 125.74, 125.00, 61.88, 61.76, 57.78, 41.89, 40.00, 37.38, 33.56, 32.61, 29.66, 28.78 , 25.91, 25.72, 20.93, 13.98 HRMS (EI) calculated for C 27 H 32 O 5 436.2250 found, 436.2242.

실시예Example 20:  20: 1-(6-1- (6- 페닐Phenyl -3--3- 옥사바이사이클로[3.1.0]핵산Oxacyclo [3.1.0] nucleic acid -1-일)-(4,5,6,7--1-yl)-(4,5,6,7- 테트라하이드로아이소벤조퓨란Tetrahydroisobenzofuran

Figure 112008060045355-pat00029
Figure 112008060045355-pat00029

시험관에 (Z)-2-(3-(3-페닐알릴록시)프로프-1-아이닐)사이클로핵스-1-앤카발데히드 (30 mg, 0.107 mmol)를 톨루엔(1 mL)에 녹인 후 자석 젓개 막대를 넣었다. 그 후 0℃에서 골드(Ⅲ) 브로마이드(2.3 mg, 0.005 mmol)를 첨가하고, 아르곤으로 시험관을 채운 후 고무격막으로 막아주었다. 그 후 상온에서 3시간 교반하였다. 그 다음 진공 증류를 통해 용매를 제거한 후 칼럼 크로마토그래피를 통해 생성물 1-(6-페닐-3-옥사바이사이클로[3.1.0]핵산-1-일)-(4,5,6,7-테트라하이드로아이소벤조퓨란 12mg (40 %)를 얻었다.Dissolve (Z) -2- (3- (3-phenylallyloxy) prop-1-ynyl) cyclonux-1-ancarbaldehyde (30 mg, 0.107 mmol) in toluene (1 mL) in a test tube. A magnetic straw bar was put. Thereafter, gold (III) bromide (2.3 mg, 0.005 mmol) was added at 0 ° C, the test tube was filled with argon, and the rubber diaphragm was blocked. Then stirred at room temperature for 3 hours. The solvent was then removed by vacuum distillation and then column chromatography to give the product 1- (6-phenyl-3-oxabicyclo [3.1.0] nucleic acid-1-yl)-(4,5,6,7-tetra 12 mg (40%) of hydroisobenzofuran were obtained.

FT-IR (neat): 2926, 2856, 1767, 1450, 1429, 1269, 1080, 1032 cm-1 1H-NMR (CDCl3): δ7.18~7.08 (m, 5H), δ6.90 (s, 1H), δ4.27~4.16 (m, 4H), δ3.09~2.89 (m, 1H), δ2.39~2.34 (m, 2H), δ2.27~2.24 (m, 2H), δ1.64~1.57 (m, 2H), δ1.46 (d, J=5.2Hz, 2H), δ1.30~1.22 (m, 7H), δ1.13 (d, J=5.6Hz, 1H); 13C-NMR (CDCl3): δ172.72, 171.63, 145.81, 140.72, 135.29,128.03, 127.81, 125.98, 122.15, 118.59, 61.87, 61.74, 57.89, 42.44, 40.05, 38.54, 33.36, 29.68, 23.32, 22.97, 21.22, 20.23, 19.73, 13.99 MS(m/z) HRMS: exact mass calculated for C26 H30O5: 280.1463. found:280.1473.FT-IR (neat): 2926, 2856, 1767, 1450, 1429, 1269, 1080, 1032 cm -1 1 H-NMR (CDCl 3 ): δ 7.18-7.08 (m, 5H), δ 6.90 (s, 1H ), δ 4.27-4.16 (m, 4H), δ 3.09-2.89 (m, 1H), δ 2.39-2.24 (m, 2H), δ 2.27-2.24 (m, 2H), δ 1.64-1.57 (m, 2H) ), δ 1.46 (d, J = 5.2 Hz, 2H), δ 1.30-1.22 (m, 7H), δ 1.13 (d, J = 5.6 Hz, 1H); 13 C-NMR (CDCl 3 ): δ 172.72, 171.63, 145.81, 140.72, 135.29,128.03, 127.81, 125.98, 122.15, 118.59, 61.87, 61.74, 57.89, 42.44, 40.05, 38.54, 33.36, 29.68, 23.32, 22.97, 22.97 21.22, 20.23, 19.73, 13.99 MS (m / z) HRMS: exact mass calculated for C 26 H 30 O 5 : 280.1463. found: 280.1473.

Claims (5)

하기 화학식 (1)로 표시되는 삼각고리를 포함하는 바이사이클로 퓨란 유도체:Bicyclo furan derivative containing a tricyclic ring represented by the following formula (1): 화학식 (1)Formula (1)
Figure 112008060045355-pat00030
Figure 112008060045355-pat00030
 상기 식에서,Where A는 탄소원자, 질소원자 또는 산소원자이고(A가 질소원자일 때, R3는 없고, A가 산소일 때, R2 및 R3는 없음), A is a carbon atom, a nitrogen atom or an oxygen atom (when A is a nitrogen atom, there is no R 3 , and when A is oxygen, there is no R 2 and R 3 ), R1 내지 R7은 각각 독립적으로, 수소원자, C1~C10의 알킬기, 알콕시, 알킬기로 에스테르화된 카르복실기, C6~C10의 아릴기, 아릴옥시기이며,R 1 To R 7 are each independently a hydrogen atom, a C 1 to C 10 alkyl group, alkoxy, a carboxyl group esterified with an alkyl group, a C 6 to C 10 aryl group, an aryloxy group, n은 1 내지 3의 정수이다.n is an integer of 1-3. 제 1항에 있어서, The method of claim 1, 상기 화학식 (1)의 화합물이 The compound of formula (1) 1-(2-(벤질옥시)-3,3-디메틸바이사이클로[3.1.0]핵산-1-일)-4,5,6,7-테트라하이드로아이소벤조퓨란; 1- (2- (benzyloxy) -3,3-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -4,5,6,7-tetrahydroisobenzofuran; 1-(2-(벤질옥시)-3,3-디메틸바이사이클로[3.1.0]핵산-1-일)-5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란; 1- (2- (benzyloxy) -3,3-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -5,6,7,8-tetrahydro-4H-cyclohapta [ c ] furan; 1-(2-(벤질옥시)-4,4-디메틸바이사이클로[3.1.0]핵산-1-일)-4,5,6,7-테트라하이드로아이소벤조퓨란; 1- (2- (benzyloxy) -4,4-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -4,5,6,7-tetrahydroisobenzofuran; 1-(2-(벤질옥시)-4,4-디메틸바이사이클로[3.1.0]핵산-1-일)-5,6,7,8-테트라하이드로-4H-사이클로햅타퓨란; 1- (2- (benzyloxy) -4,4-dimethylbicyclo [3.1.0] nucleic acid-1-yl) -5,6,7,8-tetrahydro-4H-cyclohaptafuran; 1-(2-(벤질옥시)바이사이클로[3.1.0]핵산-1-일)-4,5,6,7-테트라하이드로아이소벤조퓨란; 1- (2- (benzyloxy) bicyclo [3.1.0] nucleic acid-1-yl) -4,5,6,7-tetrahydroisobenzofuran; 1-(2-(벤질옥시)바이사이클로[3.1.0]핵산-1-일)-5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란; 1- (2- (benzyloxy) bicyclo [3.1.0] nucleic acid-1-yl) -5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan; tert-부틸디메틸(1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-2-일옥시)실란; tert-butyldimethyl (1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid-2-yloxy) silane; tert-부틸(3,3-디메틸-1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-2-일옥시)디메틸실란; tert-butyl (3,3-dimethyl-1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid-2-yloxy) dimethylsilane; 1-메틸-5-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산; 1-methyl-5- (4,5,6,7-tetrahydroisobenzofuran-1-yl) -3-tosyl-3-azabicyclo [3.1.0] nucleic acid; 1-메틸-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산; 1-methyl-5- (5,6,7,8-tetrahydro-4H-cyclohaptafuran-1-yl) -3-tosyl-3-azabicyclo [3.1.0] nucleic acid; 1-페닐-5-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산; 1-phenyl-5- (4,5,6,7-tetrahydroisobenzofuran-1-yl) -3-tosyl-3-azabicyclo [3.1.0] nucleic acid; 1-페닐-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)-3-토실-3-아자바이사이클로[3.1.0]핵산; 1-phenyl-5- (5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan-1-yl) -3-tosyl-3-azabicyclo [3.1.0] nucleic acid; 3,6-디페닐-1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)-3-아자바이사이클로[3.1.0]핵산; 3,6-diphenyl-1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) -3-azabicyclo [3.1.0] nucleic acid; 3,6-디페닐-1-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)-3-아자바이사이클로[3.1.0]핵산; 3,6-diphenyl-1- (5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan-1-yl) -3-azabicyclo [3.1.0] nucleic acid; 디에틸-1-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실레이트; Diethyl-1- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxylate; 디에틸-1-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실레이트; Diethyl-1- (5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxylate; 디에틸-1-(4,5,6,7,8,9-핵사하이드로사이클로옥타[c]퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실레이트; Diethyl-1- (4,5,6,7,8,9-nucleushydrocycloocta [ c ] furan-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxylate; 디에틸-1-페닐-5-(4,5,6,7-테트라하이드로아이소벤조퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카복실레이트; Diethyl-1-phenyl-5- (4,5,6,7-tetrahydroisobenzofuran-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxylate; 디에틸 1-페닐-5-(5,6,7,8-테트라하이드로-4H-사이클로햅타[c]퓨란-1-일)바이사이클로[3.1.0]핵산-3,3-디카르복실에이트; Diethyl 1-phenyl-5- (5,6,7,8-tetrahydro- 4H -cyclohapta [ c ] furan-1-yl) bicyclo [3.1.0] nucleic acid-3,3-dicarboxyl Eight; 1-(6-페닐-3-옥사바이사이클로[3.1.0]핵산-1-일)-(4,5,6,7-테트라하이드로아이소벤조퓨란으로 이루어진 군 중에서 선택되는 것을 특징으로 하는 바이사이클로 퓨란 유도체.Bicyclo characterized in that it is selected from the group consisting of 1- (6-phenyl-3-oxabicyclo [3.1.0] nucleic acid-1-yl)-(4,5,6,7-tetrahydroisobenzofuran Furan derivatives. 금(Au)할로겐화물을 촉매로 이용하여 하기 반응식 1에 따라 일단계의 연속적인 고리 환원반응을 통해 하기 화학식 (2)의 화합물로부터 삼각 고리를 포함하는 화학식 (1)의 바이사이클로 퓨란 유도체를 제조하는 방법:Using a gold (Au) halide as a catalyst to prepare a bicyclo furan derivative of the formula (1) comprising a tricyclic ring from the compound of the formula (2) through a one-step continuous ring reduction reaction according to Scheme 1 below How to: 반응식 1Scheme 1
Figure 112010077617733-pat00036
Figure 112010077617733-pat00036
 (2) (1)            (2) (1) 상기 식에서,Where A는 탄소원자, 질소원자 또는 산소원자이고(A가 질소원자일 때, R3는 없고, A가 산소일 때, R2 및 R3는 없음), A is a carbon atom, a nitrogen atom or an oxygen atom (when A is a nitrogen atom, there is no R 3 , and when A is oxygen, there is no R 2 and R 3 ), R1 내지 R7은 각각 독립적으로, 수소원자, C1~C10의 알킬기, 알콕시, 알킬기로 에스테르화된 카르복실기, C6~C10의 아릴기, 아릴옥시기이며,R 1 to R 7 are each independently a hydrogen atom, a C 1 to C 10 alkyl group, alkoxy, a carboxyl group esterified with an alkyl group, a C 6 to C 10 aryl group, an aryloxy group, n은 1 내지 3의 정수이다.n is an integer of 1-3. 제 3항에 있어서, The method of claim 3, 상기 화학식 (2)의 화합물이 하기 반응식 2에 따라 화학식 (3)의 화합물과 화학식 (4)의 화합물의 반응에 의해 제조되는 것을 특징으로 하는 삼각고리를 포함하는 바이사이클로 퓨란 유도체를 제조하는 방법: Method for preparing a bicyclo furan derivative comprising a tricyclic ring, characterized in that the compound of formula (2) is prepared by the reaction of a compound of formula (3) and a compound of formula (4) according to Scheme 2 below: 반응식 2Scheme 2
Figure 112008060045355-pat00032
Figure 112008060045355-pat00032
 (3) (4) (2)        (3) (4) (2) 상기 식에서, A는 탄소원자, 질소원자 또는 산소원자이고(A가 질소원자일 때, R3는 없고, A가 산소일 때, R2 및 R3는 없음), Wherein A is a carbon atom, a nitrogen atom or an oxygen atom (when A is a nitrogen atom, there is no R 3 , and when A is oxygen, there is no R 2 and R 3 ), R1 내지 R7은 각각 독립적으로, 수소원자, C1~C10의 알킬기, 알콕시, 알킬기로 에스테르화된 카르복실기, C6~C10의 아릴기, 아릴옥시기이며,R 1 To R 7 are each independently a hydrogen atom, a C 1 to C 10 alkyl group, alkoxy, a carboxyl group esterified with an alkyl group, a C 6 to C 10 aryl group, an aryloxy group, n은 1 내지 3의 정수이다.n is an integer of 1-3. 제 3항에 있어서, The method of claim 3, 상기 금(Au)할로겐화물이 골드(Ⅲ)브로마이드(AuBr3)인 것을 특징으로 하는 바이사이클로 퓨란 유도체를 제조하는 방법.The gold (Au) halide is a method of producing a bicyclo furan derivative, characterized in that the gold (III) bromide (AuBr 3 ).
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