CN107501287A - Myrtuco mmulone J和Myrtucommuacetalone及其类似物的制备方法 - Google Patents

Myrtuco mmulone J和Myrtucommuacetalone及其类似物的制备方法 Download PDF

Info

Publication number
CN107501287A
CN107501287A CN201710726182.4A CN201710726182A CN107501287A CN 107501287 A CN107501287 A CN 107501287A CN 201710726182 A CN201710726182 A CN 201710726182A CN 107501287 A CN107501287 A CN 107501287A
Authority
CN
China
Prior art keywords
compound
myrtucommuacetalone
unsaturated ketone
nmr
cdcl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201710726182.4A
Other languages
English (en)
Other versions
CN107501287B (zh
Inventor
谭海波
刘洪新
霍璐琼
王煜
徐志防
邱声祥
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
South China Botanical Garden of CAS
Original Assignee
South China Botanical Garden of CAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by South China Botanical Garden of CAS filed Critical South China Botanical Garden of CAS
Priority to CN201710726182.4A priority Critical patent/CN107501287B/zh
Publication of CN107501287A publication Critical patent/CN107501287A/zh
Application granted granted Critical
Publication of CN107501287B publication Critical patent/CN107501287B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

本发明公开了一种抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，该方法包括以下步骤：不饱和酮类化合物和单酰基间苯三酚类化合物在非极性溶剂中在三氟乙酸或醋酸或对甲苯磺酸催化剂作用下反应得到目标产物。首次实现了仿生全合成，并进一步确证了Myrtucommulone J的结构,为大量获取Myrtucommulone J和Myrtucommuacetalone及其类似物以进行后续的构效关系、成药性开发和生产，提供了一种高效可靠、经济的制备方法。

Description

Myrtuco mmulone J和Myrtucommuacetalone及其类似物的制 备方法
技术领域：
本发明涉及合成药物化学领域，具体涉及一种抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法。
背景技术：
间苯三酚类化合物结构复杂、新颖多样性及其广谱而显著的生物活性，近年来引起了合成与药物化学家们广泛的关注。Myrtucommulone J是从桃金娘科香桃木属香桃木(Myrtuscommunis)中分离发现的新颖复杂间苯三酚类化合物，抗菌活性评价表明它具有非常的显著抗菌活性，其MIC值低达0.38uM，优于临床抗菌用药最后一道屏障“万古霉素”；此外，Myrtucommulone J抗金黄色葡萄球菌的活性相较正常的人体正常细胞，具有高达35倍的选择性因子，因而具有非常明朗的成药性应用前景。Myrtucommuacetalone也是从香桃木中分离出来的抗肿瘤活性间苯三酚类天然产物，特别是对于T细胞具有非常的突出的抑制生长活性，其半致死浓度低至0.5μg/mL，被认为是开发新型抗癌新药的重要先导化合物。尽管这两个化合物具有非常新颖的结构和突出的生物活性，然后它们在自然界中含量非常的稀少，难以通过分离进行大量的获取。此外它们非常复杂的环系结构使得化学合成非常具有挑战，当前仍然没有任何化学全合成的相关报道。
发明内容：
本发明的目的是提供抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，首次实现了仿生全合成，并进一步确证了Myrtucommulone J的结构,为大量获取Myrtucommulone J和Myrtucommuacetalone及其类似物以进行后续的构效关系、成药性开发和生产，提供了一种高效可靠、经济的制备方法。
本发明是通过以下技术方案予以实现的：
抗菌化合物Myrtuco mmulone J(化合物1)和抗癌化合物Myrtucommuacetalone(化合物2)及其类似物的制备方法，该方法包括以下步骤：不饱和酮类化合物和单酰基间苯三酚类化合物在非极性溶剂中在三氟乙酸或醋酸或对甲苯磺酸催化剂作用下反应得到目标产物；所述不饱和酮类化合物选自(化合物ⅰ)，单酰基间苯三酚类化合物结构为(化合物ⅱ)，n＝0或1,R1、R2为氢、C1-C12直链烷基、C1-C12支链烷基、芳基以及含有不同活性官能团(例如含有1,3‐二酮基团)的的烷基；R3、R4为氢或烷基；其中不饱和酮类化合物(化合物ⅰ)中的虚线表示该环是六元环、五元环或带取代基的六元环、五元环。
当R3、R4为氢，其合成路线如式Ⅰ所示：
特别地，不饱和酮类化合物选自
前体化合物不饱和酮类化合物ⅰ的合成方法包括以下步骤：
1)1,3二酮与烯丙基溴在二异丙基乙胺的催化下，经过C-烷基化反应得到烯丙基化二酮；
2)步骤1)得到的中间体在对甲苯磺酸PTSA催化的条件下，发生分子内的阳离子关环即生成呋喃中间体化合物31
3)在锂铝氢还原的条件下，呋喃中间体化合物31进一步酸水解转化成目标产物化合物ⅰ。
前体化合物不饱和酮类化合物ⅰ的合成路线如式Ⅱ所示：
特别地，当不饱和酮类化合物为(化合物6)，合成路线如式Ⅲ所示：
两个类似产物化合物27和化合物28分别为Myrtucommulone J(化合物1)和Myrtucommuacetalone(化合物2)的差向异构体。
前体化合物16g的合成则通过使用1,3二酮与二溴代烷在二异丙基乙胺的催化下，经过串联的C-烷基化以及O-烷基化反应得到烯丙基化中间体33，然后再经过锂铝氢还原快速得到。
前体不饱和酮类化合物(化合物6)的合成路线如下：
包括以下步骤：
1)间苯三酚化合物19与乙酰氯在三氯化铝的催化下，经过傅克酰基化反应得到乙酰基间苯三酚；乙酰基间苯三酚在碱性条件下进行C-甲基化，然后再经过质子酸催化的逆Claisen缩合既可以得到前体化合物syncarpic acid化合物20，与烯丙基溴在二异丙基乙胺的催化下，经过C-烷基化反应得到烯丙基化中间体化合物21；
2)步骤1)得到的烯丙基化中间体化合物21再在PTSA催化的条件下，发生分子内的阳离子关环即生成四氢呋喃中间体化合物7；
3)化合物7在锂铝氢还原的条件下，进一步酸水解即可转化成仲醇化合物22；化合物22经过进一步AZADO氧化既可以顺利得到目标产物化合物6。
本发明Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone的全合成的制备方法，详细合成路线如下：
。
所述分离自桃金娘科植物的天然产物化合物3可通过不饱和酮化合物24与异丁酰基间苯三酚化合物10在碱性条件下，发生Michael加成得到，反应式如下：
所述用来合成天然产物化合物3的不饱和酮化合物24也可由syncarpic acid化合物20和异丁醛作为原料合成，合成路线为：
包括以下步骤：室温下，syncarpic acid化合物20和异丁醛化合物23在无水二氯甲烷中在三氟乙酸吗啡啉作用下得到不饱和酮化合物24。因此，本发明首次实现了仿生全合成。
本发明的有益效果如下：本发明首次实现了Myrtucommulone J和Myrtucommuacetalone的仿生全合成，并进一步确证了Myrtucommulone J的结构,为大量获取Myrtucommulone J和Myrtucommuacetalone及其类似物以进行后续的构效关系、成药性开发和生产，提供了一种高效可靠、经济的制备方法。
具体实施方式：
以下是对本发明的进一步说明，而不是对本发明的限制。
实施例1：反应条件的筛选
以不饱和酮(化合物9，0.2mmol)和异丁酰基间苯三酚(化合物10，0.2mmol)在溶剂(3mL)反应为例，考察不同溶剂、酸催化剂、反应温度的影响，具体步骤如下：
将不饱和酮(化合物9，0.2mmol)和异丁酰基间苯三酚(化合物10，0.2mmol)溶于溶剂中，向反应体系中加入三氟乙酸(50uL)或对甲苯磺酸(0.02-0.05mmol)在不同温度反应。将反应完全后的混合物经过一段约10厘米长的硅胶层析柱(正己烷：乙酸乙酯＝5:1)进行纯化，将得到相应的产物化合物11和12。波谱数据：1H NMR(500MHz,CDCl3):δ＝14.03(brs,1H),13.92(brs,1H),6.15(brs,1H),5.93(s,1H),5.83(s,1H),4.00(dt,J＝13.4,6.5Hz,1H),3.89(dt,J＝13.6,6.8Hz,1H),3.52(d,J＝2.8Hz,1H),3.47(d,J＝3.0Hz,1H),2.37-2.30(m,3H),2.28(m,1H),1.88-1.72(m,10H),1.52-1.44(m,4H),1.38(s,3H),1.37(s,3H),1.33(s,3H),1.32(s,3H),1.27(s,6H),1.21(d,J＝6.7Hz,6H),1.20(m,9H),1.17(d,J＝6.6Hz,3H)；13C NMR(125MHz,CDCl3):δ＝210.5,210.1,165.5,164.1,161.1,160.8,158.8,157.9,110.4,108.8,108.6,103.5,102.3,101.0,100.1,95.7,93.8,84.0,83.8,43.8,42.9,39.2,39.1,38.6,38.5,36.1,35.9,31.8,31.3,30.3,30.2,29.8,29.7,29.6,29.2,20.5,19.4,19.3,18.8,18.7,18.2；HRMS(ESI):calcd for C20H27O5 +,[M+H+]347.1858,found 347.1850.
结果见下表：
其中，[b]分离产率.[c]粗产物11与12的摩尔比例.[d]甲苯(2.5mL),四氢呋喃(0.5mL).[e]二氯甲烷(2.5mmol),四氢呋喃(0.5mL)
由表可知：
(1)反应在极性溶剂中很难得到产物。
(2)优选使用甲苯和四氢呋喃作为混合溶剂，产率能够高达85％以上。
(3)三氟乙酸(TFA)是已筛选的算种类中最合适的质子酸，更强或者弱的酸都会导致产率的降低。
实施例2：不同的不饱和酮化合物
合成具体步骤如下：
将不饱和酮(化合物16，0.2mmol)和异丁酰基间苯三酚(化合物10，0.2mmol)溶于甲苯/四氢呋喃混合溶液(3mL,v:v＝5:1)中，向反应体系中加入三氟乙酸(50uL)或对甲苯磺酸(0.02-0.05mmol)反应。将反应完全后的混合物经过一段约10厘米长的硅胶层析柱(正己烷：乙酸乙酯＝5:1)进行纯化，将得到相应的产物化合物17和化合物18。
1-(6,8-Dihydroxy-2,2-dimethyl-3,4,4a,5-tetrahydro-2H-5,10a-propanopyrano[2,3-b]chromen-7-yl)-2-methylpropan-1-one(化合物17a和1-(6,8-dihydroxy-2,2-dimethyl-3,4,4a,5-tetrahydro-2H-5,10a-propanopyrano[2,3-b]chromen-9-yl)-2-methylpropan-1-one(化合物18a):
1H NMR(500MHz,CDCl3):δ＝13.84(brs,1H),13.70(brs,1H),6.33(brs,1H),5.94(s,1H),5.86(s,1H),5.70(brs,1H),4.20(dt,J＝13.6,6.8Hz,1H),3.90(dt,J＝13.5,6.7Hz,1H),3.23(d,J＝2.4Hz,1H),3.19(d,J＝2.6Hz,1H),2.10(dd,J＝13.4,4.6Hz,1H),2.03-1.98(dd,J＝13.4,4.6Hz,1H),1.89-1.74(m,4H),1.73-1.39(m,16H),1.39(d,J＝4.4Hz,4H),1.29(s,3H),1.27(s,3H),1.27(s,3H),1.25(s,3H),1.20(d,J＝6.7Hz,9H),1.16(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3):δ＝210.8,210.3,165.1,163.7,161.9,159.1,158.2,103.8,103.6,103.6,102.7,102.5,101.4,95.7,93.8,74.1,74.0,39.6,39.5,39.1,39.0,38.7,36.4,36.2,33.3,32.2,31.6,31.2,27.3,21.0,20.6,20.5,19.4,19.3,19.2,19.1,17.1；HRMS(ESI):calcd for C21H29O5 +,[M+H+]361.2015,found361.2000.
1-(5,7-Dihydroxy-2,2,11,11-tetramethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-6-yl)-2-methylpropan-1-one(化合物17b)和1-(5,7-dihydroxy-2,2,11,11-tetramethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-8-yl)-2-methylpropan-1-one(化合物18b):
1H NMR(500MHz,CDCl3):δ＝14.10(s,1H),7.05(s,1H),6.70(s,1H),5.99(s,1H),5.96(s,1H),3.53(d,J＝2.8Hz,1H),3.49(d,J＝2.7Hz,1H),3.31(dd,J＝14.5,5.4Hz,1H),2.97(qd,J＝15.2,6.8Hz,2H),2.63(dd,J＝14.5,8.1Hz,1H),2.34(ddd,J＝12.6,7.3,3.0Hz,4H),2.29-2.17(m,2H),1.92-1.57(m,6H),1.49(dd,J＝19.7,7.3Hz,1H),1.46-1.41(m,1H),1.39(s,6H),1.34(s,6H),1.04(d,J＝6.7Hz,3H),1.00(d,J＝6.7Hz,6H),0.96(d,J＝6.6Hz,3H)；13C NMR(125MHz,CDCl3):δ＝206.2,205.8,165.1,163.6,161.2,160.1,158.8,158.2,108.9,108.6,104.7,104.4,102.1,100.5,95.6,93.6,84.3,83.9,53.0,52.7,43.8,43.0,38.6,38.6,36.3,36.0,31.8,31.3,30.4,30.3,29.8,29.5,29.2,25.7,25.4,23.2,22.9,22.8,22.4,18.8；HRMS(ESI):calcd for C22H31O5 +,[M+H+]375.2171,found 375.2144.
1-(5,7-Dihydroxy-2,2,12,12-tetramethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-6-yl)-2-methylpropan-1-one(化合物17c)和1-(5,7-dihydroxy-2,2,12,12-tetramethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-8-yl)-2-methylpropan-1-one(化合物18c):
1H NMR(500MHz,CDCl3):δ＝14.18(s,1H),14.06(s,1H),7.25(brs,1H),6.51(brs,1H),6.14(s,1H),5.99(s,1H),3.97(td,J＝13.7,6.8Hz,2H),3.07(d,J＝2.3Hz,1H),3.00(d,J＝2.2Hz,1H),2.71(ddd,J＝12.3,7.6,3.1Hz,2H),2.20(ddd,J＝13.0,4.8,1.7Hz,1H),2.17-2.11(m,1H),1.96-1.83(m,2H),1.76-1.68(m,2H),1.47-1.39(m,2H),1.34-1.15(m,30H),0.98-0.85(m,6H)；13C NMR(125MHz,CDCl3):δ＝210.8,210.7,165.3,165.1,161.0,160.7,158.8,157.6,109.2,108.9,103.5,101.8,100.2,95.6,94.0,85.0,84.5,39.8,39.5,39.4,39.1,38.8,38.8,38.6,37.1,32.7,32.5,32.5,31.6,30.4,30.2,29.3,29.3,28.9,28.8,25.9,25.8,22.6,20.5,19.5,19.4,18.1,14.1；HRMS(ESI):calcd forC22H31O5 +,[M+H+]375.2171,found 375.2169.
1-(6,8-Dihydroxy-2,2,13,13-tetramethyl-3,4,4a,5-tetrahydro-2H-5,10a-propanopyrano[2,3-b]chromen-7-yl)-2-methylpropan-1-one(化合物17d)和1-(6,8-dihydroxy-2,2,13,13-tetramethyl-3,4,4a,5-tetrahydro-2H-5,10a-propanopyrano[2,3-b]chromen-9-yl)-2-methylpropan-1-one(化合物18d):
化合物17d:1H NMR(500MHz,CDCl3):δ＝13.67(brs,1H),5.92(s,1H),5.30(s,1H),4.22-4.10(m,1H),2.71(s,1H),2.17-2.09(m,1H),1.90(m,2H),1.69-1.60(m,2H),1.43(m,2H),1.28-1.12(m,17H),0.86(s,3H)；13C NMR(125MHz,CDCl3):δ＝210.7,165.0,160.0,158.0,103.8,102.8,101.0,95.5,74.0,43.4,39.1,36.5,36.2,36.2,33.8,32.2,32.2,28.9,27.1,25.6,21.0,20.8,17.0；
化合物18d:1H NMR(500MHz,CDCl3):δ＝13.74(s,1H),6.31(s,1H),5.86(s,1H),3.91(dt,J＝13.4,6.7Hz,1H),2.80(s,1H),2.16(ddd,J＝9.7,7.3,2.6Hz,1H),1.90-1.79(m,2H),1.61(s,2H),1.39-1.14(m,19H),0.87(s,3H)；13C NMR(125MHz,CDCl3):δ＝210.2,164.8,161.2,158.0,103.6,103.3,102.5,94.1,74.1,43.1,39.2,36.5,36.3,36.0,34.6,32.3,32.2,31.6,29.0,26.6,25.5,22.7,20.9,19.4,19.4,14.1；HRMS(ESI):calcd forC23H33O5 +,[M+H+]389.2328,found 389.2299.
1-(5,7-Dihydroxy-2,2,10,10-tetramethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-8-yl)-2-methylpropan-1-one(化合物18e):
1H NMR(500MHz,CDCl3):δ＝13.74(brs,1H),6.31(brs,1H),5.86(s,1H),3.91(dt,J＝13.4,6.7Hz,1H),2.80(s,1H),2.16(ddd,J＝9.7,7.3,2.6Hz,1H),1.90-1.79(m,2H),1.61(s,2H),1.39-1.14(m,15H),0.87(s,3H)；13C NMR(125MHz,CDCl3):δ＝210.2,164.8,161.2,158.0,103.6,103.3,102.5,94.1,74.1,43.1,39.2,36.5,36.3,36.0,34.6,32.3,32.2,31.6,29.0,26.6,25.5,22.7,20.9,19.4,19.4,14.10(s)；HRMS(ESI):calcd forC22H31O5 +,[M+H+]375.2171,found 375.2165.
1-(6,8-Dihydroxy-2,2,11,11-tetramethyl-3,4,4a,5-tetrahydro-2H-5,10a-propanopyrano[2,3-b]chromen-7-yl)-2-methylpropan-1-one(化合物18f):
1H NMR(500MHz,CD3OD):δ＝5.90(s,1H),4.48(dt,J＝13.5,6.8Hz,1H),3.17-3.11(m,1H),2.14(ddd,J＝11.7,4.9,2.7Hz,1H),1.92(ddd,J＝13.5,8.7,4.0Hz,1H),1.66-1.53(m,3H),1.43(td,J＝13.8,4.6Hz,1H),1.38-1.26(m,3H),1.23(s,3H),1.21(s,3H),1.15-1.13(m,6H),1.12(s,3H),1.10(s,3H)；13C NMR(125MHz,CD3OD):δ＝210.9,164.7,161.6,158.3,106.9,102.6,102.3,94.6,73.0,41.2,37.4,35.5,33.5,33.3,33.0,30.9,27.3,26.6,23.0,22.7,21.0,20.2,17.1；HRMS(ESI):calcd for C23H33O5 +,[M+H+]389.2328,found 389.2288.
1-(6,8-Dihydroxy-3,4,4a,5-tetrahydro-2H-5,10a-propanopyrano[2,3-b]chromen-7-yl)-2-methyl propan-1-one(化合物17g)和1-(6,8-dihydroxy-3,4,4a,5-tetrahydro-2H-5,10a-propanopyrano[2,3-b]chromen-9-yl)-2-methyl propan-1-one(化合物18g):
1H NMR(500MHz,CDCl3):δ＝13.94(s,1H),6.63(s,1H),6.27(s,1H),5.98(s,1H),5.91(s,1H),4.13-3.73(m,6H),3.19(d,J＝2.6Hz,1H),3.15(d,J＝2.5Hz,1H),2.78-1.13(m,34H)；13C NMR(125MHz,CDCl3):δ＝210.7,165.2,159.6,158.5,103.7,101.9,101.7,96.0,62.6,62.4,39.5,39.3,38.5,38.4,34.2,33.6,33.4,31.4,30.9,25.0,23.4,20.0,19.3,19.2,19.1,19.0,18.8,18.7,18.6；HRMS(ESI):calcd for C23H33O5 +,[M+H+]389.2328,found 389.2341.
实施例3：不同的单酰基间苯三酚类化合物
当使用不同的单酰基间苯三酚类化合物13a-13f作为底物时，在三氟乙酸作为催化剂和甲苯/四氢呋喃作为混合溶剂的条件下，能够以非常良好的产率高效地得到目标类似物。
二当使用二甲酰基间苯三酚的时候，需要对甲苯磺酸作为催化剂、甲苯作为溶剂，并在加热60度的条件下才能顺利得到目标产物。
波谱数据：1-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-6-yl)etha none(化合物14a)1-(5,7-dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-8-yl)etha none(化合物15a):
1H NMR(500MHz,CDCl3):δ＝13.87(s,1H),5.97(s,1H),5.97(s,1H),3.84(ddd,J＝6.6,4.2,2.6Hz,1H),3.53(d,J＝2.8Hz,1H),3.48(d,J＝2.8Hz,1H),2.71(s,3H),2.70(s,3H),2.37-2.25(m,4H),1.94-1.91(m,1H),1.85-1.60(m,10H),1.54-1.42(m,2H),1.40(s,3H),1.39(s,3H),1.35(s,3H),1.34(s,3H)；13C NMR(125MHz,CDCl3):δ＝203.7,203.5,165.0,163.4,161.6,160.4,159.2,158.6,108.9,108.7,104.8,104.5,102.0,100.5,95.5,93.6,84.4,84.0,68.0,43.7,42.9,38.6,38.5,36.4,35.9,33.3,32.6,31.7,31.3,30.4,30.3,29.8,29.5,29.1,25.5,18.8,78.7；HRMS(ESI):calcd for C18H22O5 +,[M+H+]319.1545,found 319.1549.
1-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-6-yl)butan-1-one(化合物14b)和1-(5,7-dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-8-yl)butan-1-one(化合物15b):
1H NMR(500MHz,CDCl3):δ＝13.96(s,1H),5.94(s,1H),5.91(s,1H),3.52(d,J＝2.5Hz,1H),3.47(d,J＝2.7Hz,1H),3.29-3.21(m,1H),3.05(td,J＝7.2,2.5Hz,2H),2.95-2.84(m,1H),2.33(dd,J＝11.6,4.0Hz,3H),2.28(dd,J＝12.3,5.0Hz,1H),1.91-1.61(m,14H),1.45(m,4H),1.39(s,3H),1.38(s,3H),1.34(s,3H),1.33(s,3H),1.00(t,J＝7.4Hz,6H)；13C NMR(125MHz,CDCl3):δ＝206.4,206.0,165.1,163.7,163.5,161.1,159.6,158.6,158.3,115.0,108.8 104.4,104.4,100.3,95.6,93.6,83.9,46.3,45.9,43.7,42.9,38.6,38.5,36.3,35.9,31.8,31.3,30.4,30.3,29.8,29.5,29.1,18.8,18.7,18.4,18.2,14.0,14.0；HRMS(ESI):calcd for C20H27O5 +,[M+H+]347.1858,found 347.1850.
1-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-6-yl)hexan-1-one(化合物14c)和1-(5,7-dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-8-yl)hexan-1-one(化合物15c):
1H NMR(500MHz,CDCl3):δ＝14.04(s,1H),7.01(brs,1H),6.10(s,1H),5.98(s,1H),3.54(d,J＝2.7Hz,1H),3.48(d,J＝2.7Hz,1H),3.27(ddd,J＝15.8,8.5,6.2Hz,1H),3.15-3.02(m,2H),2.97-2.87(m,1H),2.40-2.24(m,4H),1.90-1.31(m,26H),0.92(t,J＝9.8Hz,6H)；13C NMR(125MHz,CDCl3):δ＝209.8,209.5,164.0,161.0,158.5,108.8,108.5,103.9,102.2,95.8,93.8,49.7,49.6,43.8,43.0,42.8,38.7,38.6,36.2,36.0,31.8,31.3,31.3,30.3,30.2 29.8,29.7,29.6,29.5,29.2,28.8,28.2,26.5,26.2,26.2,26.2,25.8,25.7,25.3,18.8；HRMS(ESI):calcd for C22H31O5 +,[M+H+]375.2171,found 375.2147.
Cyclohexyl(5,7-dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-6-yl)methanone(化合物14d)和cyclohexyl((5,7-dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-8-yl)methanone(化合物15d):
1H NMR(500MHz,CDCl3):δ＝14.17(brs,1H),7.07(brs,1H),6.08(s,1H),5.99(s,1H),3.73(tt,J＝11.2,3.0Hz,1H),3.65(tt,J＝11.2,3.0Hz,1H),3.53(d,J＝2.7Hz,1H),3.49(d,J＝2.7Hz,1H),2.43-2.24(m,4H),1.96(d,J＝11.0Hz,4H),1.93-1.28(m,42H)；13CNMR(125MHz,CDCl3):δ＝206.6,206.3,165.1,163.5,161.1,159.9,158.9,158.3,108.8,108.6,104.5,104.3,102.0,100.4,95.6,93.7,84.4,83.9,44.3,43.9,43.7,43.0,38.6,38.6,36.3,36.0,31.8,31.8,31.7,31.4,30.4,30.2,29.8,29.5,29.2,24.7,24.6,22.7,22.6,18.8,18.7,14.0,14.0；HRMS(ESI):calcd for C23H31O5 +,[M+H+]387.2171,found387.2164.
1-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-6-yl)-2-phenylethanone(化合物14e)和1-(5,7-dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-8-yl)-2-phenylethanone(化合物14e):
1H NMR(500MHz,CDCl3):δ＝13.87(brs,1H),13.86(brs,1H),7.47-7.13(m,10H),6.12(s,1H),5.99(s,1H),4.64(d,J＝16.5Hz,1H),4.51-4.39(m,2H),4.28(d,J＝16.5Hz,1H),3.68(s,1H),3.54(d,J＝2.7Hz,1H),3.46(d,J＝2.7Hz,1H),2.38-2.25(m,3H),2.18(dd,J＝13.0,4.7Hz,1H),1.92-1.45(m,14H),1.44(s,3H),1.40(s,3H),1.35(s,6H)；13CNMR(125MHz,CDCl3):δ＝203.3,202.9,165.3,163.7,161.6,160.6,159.1,158.3,135.7,135.6,129.9,129.7,129.4,128.7,128.3,128.3,127.3,126.6,126.5,109.3,108.7,104.5,104.2,102.1,100.7,95.7,93.9,84.6,84.0,50.4,49.8,43.7,43.0,38.7,38.6,36.2,36.0,31.7,31.3,30.5,30.2,29.8,29.7,29.5,29.2,18.8,18.6；HRMS(ESI):calcdfor C24H27O5 +,[M+H+]395.1858,found 395.1846.
1-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-6-yl)-3-methylbutan-1-one(化合物14f)和1-(5,7-dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromen-8-yl)-3-methylbutan-1-one(化合物15f):
1H NMR(500MHz,CDCl3):δ＝14.14(s,1H),7.18-6.85(brs,1H),6.03(s,1H),5.97(s,1H),4.13-4.03(m,1H),3.94(m,1H),3.51-3.42(m,1H),3.42-3.36(m,1H),2.83-2.76(m,1H),2.63(tt,J＝14.0,7.0Hz,1H),2.31(ddd,J＝12.5,7.5,2.7Hz,2H),2.18(d,J＝13.7Hz,2H),1.93-1.80(m,2H),1.80-0.67(m,38H)；13C NMR(125MHz,CDCl3):δ＝210.5,163.9,160.2,158.8,109.5,109.3,106.9,103.7,103.4,94.0,85.0,84.5,48.6,48.3,44.8,44.5,43.8,43.0,39.1,38.8,38.3,36.5,34.2,33.5,31.4,30.3,30.1,29.8,29.3,28.6,28.4,20.4,19.5,19.2,18.8,18.8,18.2；HRMS(ESI):calcd for C21H29O5 +,[M+H+]361.2015,found 361.2046.
1,1'-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromene-6,8-diyl)bis(propan-1-one)(化合物14g):
1H NMR(600MHz,CDCl3):δ＝16.32(brs,1H),15.20(brs,1H),3.58(d,J＝2.9Hz,1H),3.23(dd,J＝17.9,7.2Hz,1H),3.17(q,J＝7.2Hz,2H),3.03(dd,J＝17.9,7.2Hz,1H),2.41-2.30(m,2H),1.76(dddd,J＝54.9,40.7,16.7,13.4Hz,5H),1.43(t,J＝12.5Hz,1H),1.35(d,J＝17.4Hz,4H),1.33(d,J＝6.2Hz,3H),1.19(td,J＝7.2,1.9Hz,6H)；13C NMR(150MHz,CDCl3):δ＝207.7,207.0,170.5,168.6,162.4,110.5,104.3,102.1,100.4,84.3,43.1,38.5,37.7,37.6,36.1,31.3,30.4,29.2,29.0,18.8,8.9,8.5；HRMS(ESI):calcd forC22H29O6 +,[M+H+]389.1964,found 389.1925.
1,1'-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromene-6,8-diyl)bis(butan-1-one)(化合物14h):
1H NMR(600MHz,CDCl3):δ＝16.46(brs,1H),15.35(brs,1H),3.57(d,J＝2.9Hz,1H),3.28(dd,J＝14.5,5.4Hz,1H),3.01(ddd,J＝37.9,15.5,6.7Hz,2H),2.63(dd,J＝14.5,8.0Hz,1H),2.39-2.24(m,3H),2.21(tt,J＝13.4,6.7Hz,1H),1.89-1.61(m,4H),1.37(s,3H),1.33(s,3H),1.04(d,J＝6.7Hz,3H),1.00(d,J＝6.6Hz,6H),0.97(d,J＝6.6Hz,3H)；13C NMR(150MHz,CDCl3):δ＝206.7,206.2,170.8,169.0,162.3,110.6,104.5,102.4,100.5,84.3,53.0,52.9,43.1,38.5,36.0,31.3,30.3,29.2,29.0,25.9,24.9,23.1,22.8,22.8,22.4,18.9；HRMS(ESI):calcd for C24H33O6 +,[M+H+]417.2277,found 417.2214.
1,1'-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromene-6,8-diyl)bis(heptan-1-one)(化合物14i):
1H NMR(600MHz,CDCl3):δ＝15.26(brs,1H),3.58(d,J＝2.8Hz,1H),3.30-3.21(m,1H),3.13(td,J＝7.2,2.4Hz,2H),2.98-2.88(m,1H),2.41-2.29(m,2H),1.80(d,J＝7.3Hz,2H),1.77-1.63(m,7H),1.35(dd,J＝17.5,10.8Hz,21H),0.91(dd,J＝7.0,5.5Hz,6H)；13CNMR(150MHz,CDCl3):δ＝207.3,206.7,170.7,168.9,162.4,110.5,104.4,102.3,100.5,84.3,44.3,44.2,43.1,38.5,36.1,31.8,31.7,31.3,30.4,29.2,29.2,29.1,29.0,25.2,24.6,22.6,22.5,18.8,14.1；HRMS(ESI):calcd for C30H45O6 +,[M+H+]501.3216,found501.3238.
1,1'-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromene-6,8-diyl)bis(2-methylpropan-1-one)(化合物14j):
1H NMR(600MHz,CDCl3):δ＝15.36(brs,1H),4.08-3.96(m,2H),3.60(q,J＝2.9Hz,1H),2.43-2.29(m,2H),1.93-1.64(m,5H),1.55-1.40(m,2H),1.37(s,3H),1.34(s,3H),1.23-1.19(m,12H)；13C NMR(150MHz,CDCl3):δ＝211.6,210.9,170.8,169.3,162.0,110.5,103.7,101.4,100.6,84.3,43.12(s),39.34(s),39.2,38.5,35.9,31.2,30.2,29.3,29.0,20.6,19.2,19.1,18.9,18.3；HRMS(ESI):calcd for C24H33O6 +,[M+H+]417.2277,found417.2215.
1,1'-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromene-6,8-diyl)bis(3-methylbutan-1-one)(化合物14k):
1H NMR(600MHz,CDCl3):δ＝16.37(brs,1H),15.26(brs,1H),3.57(q,J＝2.9Hz,1H),3.23(ddd,J＝15.9,8.1,6.2Hz,1H),3.11(td,J＝7.2,3.2Hz,2H),2.95-2.87(m,1H),2.34(ddt,J＝31.0,16.9,7.8Hz,2H),1.80(dd,J＝12.2,7.4Hz,3H),1.77-1.68(m,6H),1.38(s,3H),1.33(d,J＝2.5Hz,3H),1.01(t,J＝7.4Hz,6H)；13C NMR(150MHz,CDCl3):δ＝207.1,206.5,170.7,168.8,162.3,110.5,104.4,102.2,100.4,84.3,46.2,46.1,43.01,38.5,36.0,31.3,30.3,29.2,29.0,18.8,18.6,17.9,14.0；HRMS(ESI):calcd for C26H37O6 +,[M+H+]445.2590,found 445.2587.
1,1'-(5,7-Dihydroxy-2,2-dimethyl-2,3,3a,4-tetrahydro-4,9a-propanofuro[2,3-b]chromene-6,8-diyl)bis(cyclohexylmethanone)(化合物14l):
1H NMR(500MHz,CDCl3):δ＝15.39(s,1H),3.81-3.65(m,2H),3.59(q,J＝2.8Hz,1H),2.46-2.25(m,2H),1.96-1.26(m,33H)；13C NMR(125MHz,CDCl3):δ＝210.6,209.9,171.0,169.3,162.1,118.4,110.5,103.9,101.6,100.6,84.2,49.8,49.7,43.1,38.6,36.0,31.4,31.3,30.3,29.5,29.3,29.1,28.3,26.4,26.2,26.1,26.1,26.1,25.7,18.9；HRMS(ESI):calcd for C30H41O6 +,[M+H+]497.2903,found 497.2891.
实施例4：合成Myrtucommulone J(化合物1)和Myrtucommuacetalone(化合物2)中间体化合物6的制备：
前体化合物7的制备是以间苯三酚化合物19和乙酰氯作为起始原料进行合成的。首先用间苯三酚化合物19与乙酰氯在三氯化铝的催化下，经过傅克酰基化反应得到乙酰基间苯三酚；乙酰基间苯三酚在碱性条件下进行C-甲基化，然后再经过质子酸催化的逆Claisen缩合既可以得到前体化合物syncarpic acid化合物20，与烯丙基溴在二异丙基乙胺的催化下，经过C-烷基化反应得到烯丙基化中间体化合物21。该中间体化合物21再在PTSA催化的条件下，发生分子内的阳离子关环即生成四氢呋喃中间体化合物7(如式Ⅳ所示)。化合物7在锂铝氢还原的条件下，进一步酸水解即可转化成仲醇化合物22；化合物22经过进一步AZADO氧化既可以顺利得到目标产物化合物6。
实施例5：前体化合物不饱和酮类化合物ⅰ的合成
合成路线：
包括以下步骤：
向装有1,3-二酮(化合物29，10mmol)和N,N-二异丙基乙胺(3mL)圆底烧瓶中，加入水(3mL)，均匀搅拌5分钟后，室温下向其中一次性加入烯丙基溴(化合物12或者30，11mmol)。继续搅拌反应体系5分钟后，将反应加热至60摄氏度继续搅拌3-6个小时。完全后的混合物倒入30mL的2N盐酸水溶液中，然后使用乙酸乙酯(4×40mL)萃取。萃取液合并，并用饱和食盐水洗涤，无水硫酸钠干燥，真空浓缩干燥后得到粗产物。出产物经过硅胶柱层析(硅胶，正己烷/乙酸乙酯＝2:l)，即可得到相应的烯丙基1,3-二酮。
将烯丙基1,3-二酮(10.0mmol)和甲苯(25mL)置于50mL干燥的圆底烧瓶中，加热升温至90℃。搅拌10分钟后，向反应体系中加入对甲苯磺酸(430mg,2.5mmol)。继续保持在温度下搅拌反应体系30分钟，然后冷至室温。将反应完全后的混合物经过一段约10厘米长的硅胶层析柱(正己烷：乙酸乙酯＝5:1)进行纯化，将得到相应的四氢呋喃化合物31。
将四氢呋喃化合物31(10mmol)置于50mL的无水四氢呋喃中，然后向其中慢慢加入锂铝氢(1.1g,30mmol)。紧接着将反应体系剧烈搅拌0.5个小时。向反应体系中加入丙酮5mL，继续搅拌15分钟。然后，慢慢加入饱和的酒石酸钾钠溶液10mL，收集上层有机相；瓶底沉淀用四氢呋喃洗涤2次，每次10mL。合并有机相，所得到的有机相经1N盐酸和饱和食盐水洗涤，无水硫酸钠干燥后过滤，旋转蒸发除去溶剂，得到黄棕色油状物。该油状物经过快速柱层析(正己烷：乙酸乙酯＝1:1)进一步纯化得到相应不饱和酮化合物ⅰ。
波谱数据：
2-(2-Hydroxy-2-methylpropyl)cyclohex-2-enone(化合物9):
1H NMR(600MHz,CDCl3):δ＝6.75(t,J＝4.1Hz,1H),2.36(dd,J＝9.5,3.9Hz,2H),2.33-2.30(m,2H),2.30(s,2H),1.95-1.88(m,2H),1.05(s,3H),1.04(s,3H)；13C NMR(150MHz,CDCl3):δ＝201.8,150.2,136.3,69.8 43.6,38.0,29.1,26.0,22.6；HRMS(ESI):calcd for C10H17O2 +,[M+H+]169.1229,found 169.1211.
2-(3-Hydroxy-3-methylbutyl)cyclohex-2-enone(化合物16a):
1H NMR(500MHz,CDCl3):δ＝6.76(t,J＝4.1Hz,1H),2.47-2.39(m,2H),2.39-2.31(m,2H),2.31-2.19(m,2H),1.99-1.91(m,2H),1.61-1.51(m,2H),1.23(s,6H)；13C NMR(125MHz,CDCl3):δ＝199.7,145.3,140.0,70.8,42.7,38.6,29.2,26.1,24.6,23.1；HRMS(ESI):calcd for C11H19O2 +,[M+H+]183.1385,found 183.1360.
2-(2-Hydroxy-2-methylpropyl)-5,5-dimethylcyclohex-2-enone(化合物16b):
1H NMR(500MHz,CDCl3):δ＝6.67(t,J＝4.2Hz,1H),3.42(s,1H),2.41(s,2H),2.33(s,2H),2.31(d,J＝4.2Hz,2H),1.16(s,6H),1.05(s,6H)；13C NMR(125MHz,CDCl3):δ＝202.2,147.9,135.9,70.0,51.9,43.9,40.5,34.1,29.5,28.3；HRMS(ESI):calcd forC12H21O2 +,[M+H+]197.1542,found 197.1522.
2-(2-Hydroxy-2-methylpropyl)-4,4-dimethylcyclohex-2-enone(化合物16c):
1H NMR(500MHz,CDCl3):δ＝6.49(s,1H),3.36(brs,1H),2.58-2.49(dd,J＝10.2,3.4Hz,2H),2.38(s,2H),1.89(dd,J＝10.2,3.4Hz,2H),1.20(s,6H),1.17(s,6H)；13C NMR(125MHz,CDCl3):δ＝207.1,148.2,134.9,70.0,44.4,41.6,36.2,29.5,24.3,23.4；HRMS(ESI):calcd for C12H21O2 +,[M+H+]197.1542,found 197.1528.
2-(2-hydroxy-2-methylpropyl)-6,6-dimethylcyclohex-2-enone(化合物16d):
1H NMR(500MHz,CDCl3):δ＝6.69(t,J＝4.0Hz,1H),3.42(brs,1H),2.42(dd,J＝10.7,6.0Hz,2H),2.39(s,2H),1.85(q,J＝6.2Hz,2H),1.16(s,6H),1.14(s,6H)；13C NMR(125MHz,CDCl3):δ＝207.14,148.2,134.9,70.0,44.4,41.5,36.3,29.4,27.9,24.3,23.4；HRMS(ESI):calcd for C12H21O2 +,[M+H+]197.1542,found 197.1528.
2-(3-Hydroxy-3-methylbutyl)-4,4-dimethylcyclohex-2-enone(化合物16e):
1H NMR(500MHz,CDCl3):δ＝6.42(s,1H),2.50-2.44(m,2H),2.23(ddd,J＝16.6,9.1,6.3Hz,2H),1.85(td,J＝6.9,0.6Hz,2H),1.62(brs,1H),1.59-1.52(m,2H),1.25(s,6H),1.16(s,6H)；13C NMR(125MHz,CDCl3):δ＝199.5,154.7,136.8,70.8,42.7 36.2,34.8,32.9,29.2,28.0,24.4；HRMS(ESI):calcd for C13H23O2 +,[M+H+]211.1698,found211.1659.
2-(3-Hydroxy-3-methylbutyl)-6,6-dimethylcyclohex-2-enone(化合物16f)
1H NMR(500MHz,CDCl3):δ＝6.65(t,J＝4.1Hz,1H),4.74(s,1H),2.37(tdt,J＝5.8,4.1,1.3Hz,2H),2.29-2.23(m,2H),1.83(t,J＝6.1Hz,2H),1.69(s,2H),1.63(s,1H),1.57-1.50(m,2H),1.25(s,6H),1.12(s,6H)；13C NMR(125MHz,CDCl3):δ＝204.6,143.2,138.0,70.8,42.9,41.3,36.4,29.2,25.2,24.2,23.1；HRMS(ESI):calcd for C13H23O2 +,[M+H+]211.1698,found 211.1647.
2-(3-hydroxypropyl)cyclohex-2-enone化合物16g:
1H NMR(500MHz,CDCl3):δ＝6.81(t,J＝3.9Hz,1H),3.57(t,J＝6.2Hz,2H),2.50-2.40(m,2H),2.37(dd,J＝10.3,5.6Hz,2H),2.29(t,J＝7.1Hz,2H),2.06-1.93(m,3H),1.75-1.60(m,3H)；13C NMR(125MHz,CDCl3):δ＝200.4,146.7,139.3,77.3,77.0,76.8,61.5,38.4,32.2,26.1,25.4,23.1；HRMS(ESI):calcd for C9H15O2 +,[M+H+]155.1072,found155.1056.
实施例6：Myrtuco mmulone J(化合物1)和抗癌化合物Myrtucommuacetalone(化合物2)的全合成
乙酰基间苯三酚化合物35的合成
在冰浴条件下，将三氯化铝(13.3g,100mmol)慢慢地加入到间苯三酚化合物19(3.15g，25mmol)的1,2-二氯乙烷/硝基甲苯混合溶液(1:1,50mL)中。均匀搅拌10分钟后，向反应体系中慢慢滴加乙酰氯化合物34(2.38mg,30mmol)。撤除冰浴条件，紧接着将反应混合物加热至80摄氏度并搅拌3个小时。然后加入150mL水终止反应。混合物用乙酸乙酯(150mL)萃取5次，合并有机相。所得到的有机相用50mL饱和食盐水洗涤，无水硫酸钠干燥，过滤。剩余物经过快速柱层析(正己烷：乙酸乙酯＝2:1)进一步纯化得到浅黄色固体化合物化合物35(3.32g,79％yield)。1H NMR(500MHz,DMSO-d6):δ＝5.81(s,2H),2.54(s,3H)；13C NMR(125MHz,DMSO-d6):δ＝203.9,166.2,164.7,105.9,96.3,33.5.
乙酰基β-三酮化合物36的合成:
在冰浴条件下，将乙酰基间苯三酚化合物35(5.5g,30mmol)溶于120mL无水的甲醇溶液中，然后慢慢地加入甲醇钠(14.4g，266mmol)。均匀搅拌10分钟后，向反应体系中慢慢滴加碘甲烷(14.2mL，228mmol)。继续在冰浴条件下搅拌30分钟，紧接着将反应混合物置于室温下搅拌24个小时。然后加入150mL 2N的盐酸水溶液终止反应。混合物用乙酸乙酯(150mL)萃取4次，合并有机相。所得到的有机相用50mL饱和食盐水洗涤，无水硫酸钠干燥，过滤。剩余物经过快速柱层析(正己烷：乙酸乙酯＝5:1)进一步纯化得到3.17g无色油状化合物化合物36,产率86％浅棕色片状固体。1H NMR(500MHz,CDCl3):δ＝2.57(s,3H),1.42(s,6H),1.33(s,6H)；13C NMR(125MHz,CDCl3):δ＝210.0,201.7,199.1,196.7,109.4,56.7,52.0,27.4,24.3,23.8.
5-hydroxy-2,2,6,6-tetramethylcyclohex-4-ene-1,3-dione(syncarpic acid)化合物20的合成:
将乙酰基β-三酮化合物36(6.36g,28.5mmol)置于250mL的圆底烧瓶中，然后向其中加入6N的盐酸水溶液120mL。紧接着将反应体系置于120℃油浴中，剧烈搅拌并加热回流24个小时。待反应体系逐渐降至室温，然后将反应混合物用乙酸乙酯(150mL)萃取4次，合并有机相。所得到的有机相经无水硫酸钠干燥后过滤，旋转蒸发除去溶剂后，得到黄棕色油状物。该油状物经过快速柱层析(正己烷：乙酸乙酯＝1:1)进一步纯化得到4.05g浅棕色粉末状固体化合物syncapic acid(化合物20)，产率78％。20：黄棕色粉末状固体；酮/烯醇异构的混合物，比例约为2:1。1H NMR(500MHz,CDCl3):ketone:δ＝3.61(s,2H),1.31(s,12H)；enol:δ＝8.00(br s,1H),5.74(brd,J＝2.3Hz,1H),1.40(s,12H)；13C NMR(125MHz,CDCl3):ketone:δ＝208.9,59.1,50.2,21.8；enol:δ＝212.6,204.3,191.6,101.7,59.1,51.2,24.5.
2,2,4,4-tetramethyl-6-(2-methylpropylidene)cyclohexane-1,3,5-trione化合物24的合成:
向装有syncapic acid化合物20(182mg,1.0mmol)和异丁醛(216mg,3.0mmol)的20mL圆底烧瓶中加于无水二氯甲烷(10mL)，均匀搅拌5分钟后，室温下向其中一次性加入三氟乙酸吗啡啉(20mg,0.1mmol)。继续搅拌反应体系半个小时后，将反应完全后的混合物经过一段约3厘米长的硅胶层析柱(二氯甲烷作为洗脱剂)进行纯化，将能以当量的收率得到224mg无色油状化合物化合物24。1H NMR(500MHz,CDCl3):δ＝7.24(d,J＝10.5Hz,1H),3.35(m,1H),1.31(s,6H),1.30(s,6H),1.10(d,J＝6.6Hz,6H)；13C NMR(125MHz,CDCl3):δ＝208.7,199.7,196.5,164.8,28.5,130.6,58.5,58.1,22.3,21.9,21.8.
5-hydroxy-2,2,6,6-tetramethyl-4-(2-methylallyl)cyclohex-4-ene-1,3-dione化合物21的合成:
向装有syncapic acid化合物20(1.82g,1.0mmol)和N,N-二异丙基乙胺(10mL)圆底烧瓶中，加入水(10mL)，均匀搅拌5分钟后，室温下向其中一次性加入2-甲基烯丙基溴化合物12(0.67g,5mmol)。继续搅拌反应体系5分钟后，将反应加热至90摄氏度继续搅拌6个小时。反应完全后的混合物倒入80mL的2N盐酸水溶液中，然后使用乙酸乙酯(4×100mL)萃取。萃取液合并，并用饱和食盐水洗涤，无水硫酸钠干燥，真空浓缩干燥后得到粗产物。出产物经过硅胶柱层析(硅胶，正己烷/乙酸乙酯＝5:l)，即可得到相应的烯丙基1,3-二酮化合物21(0.85g,72％产率)。1H NMR(500MHz,CDCl3):δ＝6.83(s,1H),5.02(d,J＝0.5Hz,1H),4.99(s,1H),3.29(s,2H),1.74(s,3H),1.45(s,7H),1.37(s,7H)；13C NMR(125MHz,CDCl3):δ＝212.8,204.3,197.8,173.2,145.0,113.0,111.0,109.0,60.3,58.5,55.3,47.9,31.7,30.5,24.9,24.6,24.5,24.3,23.1,23.0,22.5,21.3；HRMS(ESI):calcd for C14H21O3 +,[M+H+]237.1491,found 237.1487.
四氢呋喃化合物化合物7的合成:
将烯丙基1,3-二酮化合物21(0.85g,3.6mmol)和甲苯(15mL)置于50mL干燥的圆底烧瓶中，加热升温至90℃。搅拌10分钟后，向反应体系中加入对甲苯磺酸(209mg,1.1mmol)。继续保持在温度下搅拌反应体系30分钟，然后冷至室温。将反应完全后的混合物经过一段约10厘米长的硅胶层析柱(正己烷：乙酸乙酯＝5:1)进行纯化，将得到相应的四氢呋喃化合物化合物7(0.78g,92％产率)。1H NMR(500MHz,CDCl3):δ＝2.76(s,1H),1.49(s,3H),1.40(s,4H),1.36(s,3H)；13C NMR(125MHz,CDCl3):δ＝213.0,193.9,175.5,108.4,89.8,54.1,44.3,38.6,27.1,23.6,23.2；HRMS(ESI):calcd for C14H21O3 +,[M+H+]237.1491,found237.1485.
仲醇化合物22的合成
将四氢呋喃化合物化合物7(236mg,1.0mmol)置于10mL的无水四氢呋喃中，然后向其中慢慢加入锂铝氢(104mg,3.0mmol)。紧接着将反应体系剧烈搅拌0.5个小时。向反应体系中加入丙酮1mL，继续搅拌15分钟。然后，慢慢加入饱和的酒石酸钾钠溶液10mL，收集上层有机相；瓶底沉淀用四氢呋喃洗涤2次，每次10mL。合并有机相，所得到的有机相经1N盐酸和饱和食盐水洗涤，无水硫酸钠干燥后过滤，旋转蒸发除去溶剂，得到黄棕色油状物。该油状物经过快速柱层析(正己烷：乙酸乙酯＝1:1)进一步纯化，得到仲醇化合物22(207mg,87％yield)。1H NMR(500MHz,CDCl3):δ＝6.42(s,1H),3.54(s,1H),3.36(s,1H),2.50(s,1H),2.40(q,J＝13.8Hz,2H),1.24-1.20(m,9H),1.18(s,3H),1.14(s,3H),1.12(s,3H)；13C NMR(125MHz,CDCl3):δ＝206.7,156.3,131.2,79.2,70.2,47.9,44.0,38.4,30.2,29.6,29.1,23.6,21.5,20.6；HRMS(ESI):calcd for C14H25O3 +,[M+H+]241.1804,found 241.1806.
不饱和酮化合物6的合成:
向含有叔醇化合物22(207mg,0.87mmol)、AZADO(0.14mg,0.87μmol)、溴化钾(10.3mg,0.087M)以及四丁基溴化铵(14.0mg,0.044M)的二氯甲烷(2mL)和饱和碳酸氢钠(1mL)的混合溶液中，在0摄氏度的条件下，慢慢滴加次氯酸钠与饱和碳酸氢钠的混合溶剂(1.8mL,1:1.4v/v)，控制滴加时间为10分钟左右。剧烈搅拌反应混合体系5分钟后，使用2mL饱和硫代硫酸钠溶液与22mL水淬灭。水相经过乙酸乙酯(4×10mL)萃取，合并有机相，饱和食盐水洗涤，无水硫酸钠干燥后过滤，旋转蒸发除去溶剂，得到黄棕色油状物。该油状物经过快速柱层析(正己烷：乙酸乙酯＝1:1)进一步纯化得到相应不饱和酮化合物化合物6(185mg,90％yield)。1H NMR(500MHz,CDCl3):δ＝6.61(s,1H),2.71(brs,1H),2.54(s,2H),1.38(s,6H),1.36(s,6H),1.23(s,6H)；13C NMR(125MHz,CDCl3):δ＝213.1,203.4,152.7,132.3,70.3,57.5,45.2,43.8,29.5,27.4,23.9；HRMS(ESI):calcd for C14H23O3 +,[M+H+]239.1647,found 239.1614.
化合物3的合成:
氢化钠(152mg,3.8mmol,60％矿物油中)慢慢地加入溶有酰基间苯三酚化合物10(372mg,1.90mmol)的四氢呋喃溶液(10mL)中，然后加入溶有不饱和酮化合物24(224mg,0.95mmol)的四氢呋喃溶液(5mL)。混合物于室温下搅拌半个小时后，加入15mL 2N的盐酸水溶液。分离有机相，水相经乙酸乙酯(15mL)萃取3次，饱和食盐水(15mL)洗涤，无水硫酸钠干燥，旋转蒸发出去剩余的有机溶剂。剩余的粗产物再经过硅胶柱分离(正己烷：乙酸乙酯＝10:1-2:1)，将能以87％的产率得到所需要的目标产物化合物3(357mg)。1H NMR(500MHz,CDCl3):δ＝11.58(s,1H),11.25(s,1H),10.52(s,1H),10.41(s,1H),6.87(s,1H),6.02(s,1H),5.96(s,1H),4.01-3.89(m,2H),3.83-3.73(m,2H),3.10(m,1H),3.05-2.94(m,1H),2.60(dd,J＝14.0,7.0Hz,2H),1.50(s,6H),1.43(s,3H),1.39(s,3H),1.38(s,3H),1.36(s,3H),1.33(s,6H),1.26-1.16(m,12H),0.89(d,J＝6.4Hz,3H),0.85(d,J＝6.3Hz,3H),0.81(d,J＝6.3Hz,3H),0.77(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3):δ＝212.85(s),211.6,211.1,203.5,202.9,182.7,178.2,164.0,163.7,163.6,163.5,158.8,114.3,114.2,109.0,108.6,102.8,97.9,97.8,54.9,54.3,49.0,48.8,40.2,39.1,39.0,38.9,33.7,26.5,26.5,26.0,26.0,25.9,25.5,24.8,24.7,24.1,23.4,22.0,22.0,21.7,19.9.2,18.7.
The synthesis of Myrtucommulone J(1),Myrtucommuuacetalone(2),epi-Myrtucommulone J(27),and epi-Myrtucommuuacetalone(28):
将间苯三酚化合物3(260mg,0.6mmol)和不饱和酮化合物6(119mg,0.5mmol)加于甲苯(6mL)，并加热至90摄氏度，然后向反应体系中加入对甲苯磺酸(43mg,0.25mmol)。继续保持在室温下搅拌反应体系24小时。然后停止搅拌，反应混合液经过一段约10厘米长的硅胶层析柱(正己烷：乙酸乙酯＝5:1)进行纯化，将能以89的总产率得到相应产物Myrtucommulone J(化合物1),Myrtucommuuacetalone(化合物2),epi-Myrtucommulone J(化合物27),and epi-Myrtucommuuacetalone(化合物28)，它们的摩尔比约为1:1.7:1.4:1.2。
Myrtucommulone J(化合物1):1H NMR(500MHz,CDCl3):δ＝14.32(s,1H),11.92(s,1H),9.17(s,1H),4.09(ddd,J＝14.9,11.1,5.1Hz,1H),3.52(m,1H),3.46(m,1H),3.40(d,J＝3.2Hz,1H),2.96(dq,J＝17.0,6.3Hz,1H),1.96(dd,J＝12.2,7.0Hz,1H),1.59((dd,J＝12.2,7.0Hz,1H),1.53(s,3H),1.53(3H,s),1.45(s,3H),1.45(s,3H),1.42(s,3H),1.41(s,6H),1.39(s,3H),1.36(s,6H),1.25(d,J＝6.7Hz,3,),1.17(d,J＝6.7Hz,3H),0.94(s,3H),0.80(d,J＝6.3Hz,3H),0.55(d,J＝6.3Hz,3H)；13C NMR(125MHz,CDCl3):δ＝216.9,212.4,21.2.1,203.1,177.6,163.4,159.4,154.8,115.5,114.1,105.5,105.0,99.9,86.7,54.9,54.0,51.1,48.7,40.5,39.6,38.9,36.8,35.4,31.6,30.5,28.8,28.3,26.5,25.5,25.4,24.6,24.5,23.6,22.6,22.1,21.7,19.7,19.4,19.2；HRMS(ESI):calcd for C38H53O9 +,[M+H+]653.3690,found 653.3678.
Myrtucommuuacetalone(化合物2):1H NMR(500MHz,CDCl3):δ＝11.76(s,1H),11.26(s,1H),10.63(s,1H),10.51(s,1H),4.12(1H,hept,J＝6.6Hz),4.11(ddd,J＝17.6,13.4,6.7Hz,1H),3.87(d,J＝11.2Hz,1H),3.77(d,J＝10.9Hz,1H),3.50-3.37(m,4H),3.18-3.08(m,1H),3.04-2.93(m,1H),1.95(dd,J＝12.4,7.1Hz,1H),1.89(dd,J＝12.2,7.4Hz,1H),1.53(s,3H),1.46(s,3H),1.43(s,3H),1.41(s,3H),1.37(s,6H),1.36(s,3H),1.35(s,6H),1.32(s,3H),1.19(d,J＝6.6Hz,3H),1.17(d,J＝6.6Hz,3H),1.07(3H,s),0.85(d,J＝6.3Hz,3H),0.72(d,J＝6.3Hz,3H)；13C NMR(126MHz,CDCl3)δ＝217.8,217.5,212.6,212.5,212.0,211.5,203.4,203.0,178.3,177.3,162.6,162.4,162.0,161.9,154.3,154.2,114.3,114.2,114.1,114.0,108.6,108.3,103.4,103.2,102.7,102.3,85.1,84.9,55.0,54.2,53.9,50.0,55.0,49.1,48.8,40.2,39.3,39.3,38.1,37.8,37.7,37.6,35.2,35.0,30.2,29.7,29.0,28.6,26.8,26.5,26.0,25.7,25.6,25.2,24.8,24.6,24.2,23.7,23.2,23.1,22.0,21.6,20.8,20.2,19.6,19.0；HRMS(ESI):calcd for C38H53O9 +,[M+H+]653.3690,found 653.3640.
Epi-Myrtucommulone J(化合物27):1H NMR(500MHz,CDCl3):δ＝14.27(s,1H),14.22(s,1H),11.78(s,1H),11.05(s,1H),9.67(s,1H),8.59(s,1H),4.23-4.08(m,2H),3.80(d,J＝11.3Hz,1H),3.58(m,1H),3.50-3.45(m,2H),3.43(t,J＝5.4Hz,1H),3.33(d,J＝10.7Hz,1H),2.93-2.79(m,2H),2.00-1.88(m,2H),1.61-0.53(m,90H)；13C NMR(125MHz,CDCl3):δ＝217.3,216.6,212.4,212.4,212.1,203.9,202.5,184.3,176.3,163.6,162.7,159.5,159.4,156.1,155.3,117.9,115.3,114.4,114.0,105.8,105.7,104.2,101.6,100.2,86.9,85.9,54.9,54.3,53.4,50.2,50.1,49.2,48.4,41.5,40.4,39.6,38.9,38.8,36.9,36.5,35.8,35.1,30.8,30.5,29.3,28.5,28.4,28.1,27.3,26.7,26.0,25.8,25.5,25.5,25.4,25.3,25.2,25.1,24.5,24.3,23.8,22.2,22.0,21.7,21.5,20.1,19.7,19.6,19.5,19.3,19.2；HRMS(ESI):calcd for C38H53O9 +,[M+H+]653.3690,found 653.3653.
Epi-Myrtucommuuacetalone(化合物28):1H NMR(500MHz,CDCl3)δ＝11.58(s,1H),11.46(s,1H),10.84(s,1H),10.41(s,1H),4.14(dt,J＝13.5,6.7Hz,1H),4.08(dt,J＝13.4,6.8Hz,1H),3.86-3.77(m,1H),3.74(t,J＝7.6Hz,1H),3.50-3.38(m,4H),3.15-2.94(m,2H),1.93(ddd,J＝26.2,12.3,7.4Hz,2H),1.53(s,3H),1.52(s,3H),1.43-1.25(m,31H),1.23-1.13(m,12H),1.04(s,3H),0.94-0.81(m,9H),0.77(d,J＝6.5Hz,3H),0.72(d,J＝6.3Hz,3H)；13C NMR(125MHz,CDCl3):δ＝217.7,217.6,212.8,212.4,212.0,211.5,203.8,203.1,178.7,176.8,162.9,162.7,162.3,161.9,154.3,114.1,114.0,108.7,108.1,103.5,102.6,102.3,85.0,54.7,54.4,53.9,53.8,50.2,49.9,49.1,48.8,41.2,39.4,39.3,39.2,37.9,37.8,37.8,37.7,35.3,34.9,30.2,30.1,29.0,28.6,28.6,26.7,26.5,26.1,26.0,25.4,25.2,25.0,24.7,24.6,24.5,24.4,23.7,23.4,23.2,22.0,22.0,22.0,21.9,20.7,20.3,19.6,19.4,19.0.HRMS(ESI):calcd for C38H53O9 +,[M+H+]653.3690,found 653.3651.
本专利通过分析比较这两个天然产物的结构与谱图特征，认为文献中报道的Myrtucommulone J(化合物1)的结构需要进行修正，其正确的应该如本发明所示。

Claims (8)

1.抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，其特征在于，该方法包括以下步骤：不饱和酮类化合物和单酰基间苯三酚类化合物在非极性溶剂中在三氟乙酸或醋酸或对甲苯磺酸催化剂作用下反应得到目标产物，所述不饱和酮类化合物选自单酰基间苯三酚类化合物结构为n＝0或1,R1、R2为氢、C1-C12直链烷基、C1-C12支链烷基、芳基以及含有不同活性官能团的烷基，R3、R4为氢或烷基；其中不饱和酮类化合物中的虚线表示该环是六元环、五元环或带取代基的六元环、五元环。
2.根据权利要求1所述的抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，其特征在于，合成路线如式Ⅰ所示：
3.根据权利要求1或2所述的抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，其特征在于，不饱和酮类化合物选自
4.根据权利要求1所述的抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，其特征在于，不饱和酮类化合物的合成方法包括以下步骤：
1)1,3二酮与烯丙基溴在二异丙基乙胺的催化下，经过C-烷基化反应得到烯丙基化二酮；
2)步骤1)得到的中间体在对甲苯磺酸PTSA催化的条件下，发生分子内的阳离子关环即生成呋喃中间体化合物31。
3)在锂铝氢还原的条件下，呋喃中间体化合物31进一步酸水解转化成目标产物化合物ⅰ；
前体化合物不饱和酮类化合物ⅰ的合成路线如式Ⅱ所示：
5.根据权利要求3所述的抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，其特征在于，不饱和酮类化合物为时，合成路线如式Ⅲ所示：
6.根据权利要求5所述的抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，其特征在于，不饱和酮类化合物的合成路线如下：
；
包括以下步骤：
1)间苯三酚化合物19与乙酰氯在三氯化铝的催化下，经过傅克酰基化反应得到乙酰基间苯三酚；乙酰基间苯三酚在碱性条件下进行C-甲基化，然后再经过质子酸催化的逆Claisen缩合既可以得到前体化合物syncarpic acid化合物20，与烯丙基溴在二异丙基乙胺的催化下，经过C-烷基化反应得到烯丙基化中间体化合物21；
2)步骤1)得到的烯丙基化中间体化合物21再在PTSA催化的条件下，发生分子内的阳离子关环即生成四氢呋喃中间体化合物7；
3)化合物7在锂铝氢还原的条件下，进一步酸水解即可转化成仲醇化合物22；化合物22经过进一步AZADO氧化既可以顺利得到目标产物化合物6。
7.根据权利要求5所述的抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，其特征在于，所述分离自桃金娘科植物的天然产物化合物3可通过不饱和酮化合物24与异丁酰基间苯三酚化合物10在碱性条件下，发生Michael加成得到，反应式如下：
8.根据权利要求7所述的抗菌化合物Myrtuco mmulone J和抗癌化合物Myrtucommuacetalone及其类似物的制备方法，其特征在于，所述用来合成天然产物化合物3的不饱和酮化合物24由syncarpic acid化合物20和异丁醛作为原料合成，合成路线为：
包括以下步骤：室温下，syncarpic acid化合物20和异丁醛化合物23在无水二氯甲烷中在三氟乙酸吗啡啉作用下得到不饱和酮化合物24。
CN201710726182.4A 2017-08-22 2017-08-22 Myrtuco mmulone J和Myrtucommuacetalone及其类似物的制备方法 Active CN107501287B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710726182.4A CN107501287B (zh) 2017-08-22 2017-08-22 Myrtuco mmulone J和Myrtucommuacetalone及其类似物的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710726182.4A CN107501287B (zh) 2017-08-22 2017-08-22 Myrtuco mmulone J和Myrtucommuacetalone及其类似物的制备方法

Publications (2)

Publication Number Publication Date
CN107501287A true CN107501287A (zh) 2017-12-22
CN107501287B CN107501287B (zh) 2019-09-13

Family

ID=60692210

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710726182.4A Active CN107501287B (zh) 2017-08-22 2017-08-22 Myrtuco mmulone J和Myrtucommuacetalone及其类似物的制备方法

Country Status (1)

Country Link
CN (1) CN107501287B (zh)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111348980A (zh) * 2019-11-18 2020-06-30 宁波大学 一种可见光驱动的1,6-烯炔与磺酰氯的磺酰化/环化反应方法
CN112920156A (zh) * 2019-12-05 2021-06-08 中国科学院大连化学物理研究所 一种酸催化环1,3-二酮异戊烯基化反应的方法
CN113929570A (zh) * 2021-11-02 2022-01-14 湖南中嘉生物医药有限公司 一种桃金娘酮衍生物及其制备方法和用途
WO2024083551A1 (en) * 2022-10-21 2024-04-25 International Flavors & Fragrances Inc. Process of making 2,2,6,6,7,8,8-heptamethyl-3,6,7,8-tetrahydro-2h-indeno[4,5-b]furan and its uses

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103638012A (zh) * 2013-12-04 2014-03-19 常州科立信医疗器械有限公司 Myrtucommuacetalone在治疗心肌缺血药物中的应用
CN103655549A (zh) * 2013-12-05 2014-03-26 常州科立信医疗器械有限公司 Myrtucommuacetalone在治疗或预防急性心衰药物中的应用
CN103705504A (zh) * 2013-12-05 2014-04-09 常州科立信医疗器械有限公司 Myrtucommuacetalone在治疗缺血性脑损伤药物中的应用
CN104761565A (zh) * 2015-04-16 2015-07-08 中国科学院华南植物园 桃金娘酮化合物及其在制备抗菌药物中的应用
CN105622379A (zh) * 2016-03-15 2016-06-01 中国科学院华南植物园 2,4-二乙酰基间苯三酚类似物及其制备方法和应用
CN105859537A (zh) * 2016-04-27 2016-08-17 中国科学院华南植物园 开环桃金娘酮类似物及其制备方法和在抗菌药物中的应用
CN106986852A (zh) * 2017-04-13 2017-07-28 暨南大学 Myrtucommulone R及其在制备抗菌药物中的应用

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103638012A (zh) * 2013-12-04 2014-03-19 常州科立信医疗器械有限公司 Myrtucommuacetalone在治疗心肌缺血药物中的应用
CN103655549A (zh) * 2013-12-05 2014-03-26 常州科立信医疗器械有限公司 Myrtucommuacetalone在治疗或预防急性心衰药物中的应用
CN103705504A (zh) * 2013-12-05 2014-04-09 常州科立信医疗器械有限公司 Myrtucommuacetalone在治疗缺血性脑损伤药物中的应用
CN104761565A (zh) * 2015-04-16 2015-07-08 中国科学院华南植物园 桃金娘酮化合物及其在制备抗菌药物中的应用
CN105622379A (zh) * 2016-03-15 2016-06-01 中国科学院华南植物园 2,4-二乙酰基间苯三酚类似物及其制备方法和应用
CN105859537A (zh) * 2016-04-27 2016-08-17 中国科学院华南植物园 开环桃金娘酮类似物及其制备方法和在抗菌药物中的应用
CN106986852A (zh) * 2017-04-13 2017-07-28 暨南大学 Myrtucommulone R及其在制备抗菌药物中的应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HONGXIN LIU ET AL: "Biomimetic-Inspired Syntheses of Myrtucommuacetalone and Myrtucommulone J", 《ORGANIC LETTERS》 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111348980A (zh) * 2019-11-18 2020-06-30 宁波大学 一种可见光驱动的1,6-烯炔与磺酰氯的磺酰化/环化反应方法
CN111348980B (zh) * 2019-11-18 2023-05-02 宁波大学 一种可见光驱动的1,6-烯炔与磺酰氯的磺酰化/环化反应方法
CN112920156A (zh) * 2019-12-05 2021-06-08 中国科学院大连化学物理研究所 一种酸催化环1,3-二酮异戊烯基化反应的方法
CN112920156B (zh) * 2019-12-05 2023-02-28 中国科学院大连化学物理研究所 一种酸催化环1,3-二酮异戊烯基化反应的方法
CN113929570A (zh) * 2021-11-02 2022-01-14 湖南中嘉生物医药有限公司 一种桃金娘酮衍生物及其制备方法和用途
CN113929570B (zh) * 2021-11-02 2024-01-30 湖南中嘉生物医药有限公司 一种桃金娘酮衍生物及其制备方法和用途
WO2024083551A1 (en) * 2022-10-21 2024-04-25 International Flavors & Fragrances Inc. Process of making 2,2,6,6,7,8,8-heptamethyl-3,6,7,8-tetrahydro-2h-indeno[4,5-b]furan and its uses

Also Published As

Publication number Publication date
CN107501287B (zh) 2019-09-13

Similar Documents

Publication Publication Date Title
CN107501287B (zh) Myrtuco mmulone J和Myrtucommuacetalone及其类似物的制备方法
Molander et al. Synthesis of Substituted Cyclooctanols by a Samarium (II) Iodide Promoted 8-Endo Radical Cyclization Process
CN1266145C (zh) 大麻化合物的合成
RU2727202C2 (ru) Улучшенный синтез гонокиола
US11168064B2 (en) Synthesis of thapsigargin, nortrilobolide, and analogs thereof
CN102503788A (zh) 4-(2-甲基烯丙基)-1,2-苯二酚作为制备香料的应用
Perron-Sierra et al. Novel bicyclic oxazolone derivatives as anti-angiogenic agents
CN102344431B (zh) 一种制备奈必洛尔盐酸盐的方法
CN103664985B (zh) β型羟基青蒿烷基醚的立体选择性制备方法
ES2396524B2 (es) Intermedios versátiles y funcionalizados en la síntesis de vitamina D y nuevos derivados de vitamina D
CN113072576B (zh) 一类手性硅代松叶菊碱、合成方法及用途
Lemus et al. Lewis acid catalyzed enlargement of cyclic β‐alkoxyenals and one‐pot synthesis of polyfunctional enoxysilanes derived from aucubin with trimethylsilyldiazomethane
EP0901492A1 (en) Taxane derivatives, the preparation thereof and formulations containing them
CN103360352A (zh) 4-甲氧基-2,6-二羟基-2-苄基-3(2h)-苯并呋喃酮的全合成方法
Vida et al. Cyclophane size drives the photochemical behaviour of benzophenone
US6872840B1 (en) Synthesis of 8-membered carbocyclic compound having diexomethylene groups
Li et al. Enantioselective total synthesis of chiricanine B
Vlad et al. Asymmetric dihydroxylation of drim-7-en-11-ol: synthesis of diastereomerically pure driman-7α, 8α, 11-triol and its elaboration into novel chlorinated norlabdanic compounds
CN106565644A (zh) 3‑烷基‑5‑羟基‑4‑芳基呋喃酮衍生物及其制备方法
Ottenbruch Studies Toward the Total Synthesis of Taxpropellane
Meng Enantioselective Synthesis of Chromanone and Thiochromanone Derivatives
CN101830872A (zh) 一种3-羟基苯并呋喃类衍生物的合成方法
KR100941736B1 (ko) 다이하이드로 퓨란 유도체와 금 촉매를 이용한 이의 합성
CN101293851B (zh) (z)-2-苯甲酰基氨基-4，4-二氟-2-丁烯酸乙酯、顺式1-苯甲酰基氨基-2-二氟甲基环丙烷甲酸乙酯及其合成方法
CN116655590A (zh) 一种共轭多烯化合物及其制备方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant