JP2007063247A - New method of manufacturing unsaturated large cyclic lactone - Google Patents
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Abstract
Description
本発明は不飽和大環状ラクトンの製造法に関するもので，化粧品，香粧品，食品等の属する分野および他の分野において要求されている香料の製造に供するものである。 The present invention relates to a method for producing an unsaturated macrocyclic lactone, and is used for the production of a perfume required in the fields to which cosmetics, cosmetics, foods and the like belong and other fields.
香料は化粧品，香粧品，食品等に添加され，香気を付与し，化粧品，香粧品，食品等の付加価値を高めるために頻繁に使用されている。中でも，天然香料の一つとして知られているムスクは古くから珍重されており，現在でも高い需要がある。しかしながら，ムスクの供給源である雄のジャコウジカなどの動物は乱獲により絶滅の危機に瀕しており，今日では天然ムスクは入手困難となっている。ムスクの香気成分は大環状ケトンのムスコンやシベトンなどで，その類縁体もムスク様の香気を有する。また，トロロアオイモドキの種子やアンゲリカの種子から得られる大環状ラクトンである（７Ｚ）−アンブレットリド，およびシクロペンタデカノリドはそれぞれムスク様の香気を有し，ムスクの良い代替品となる。しかしながら，植物からの供給量は天候などに影響されやすく，年度あるいは季節ごとに大きく変動する。そこで，これら大環状ラクトンを人工的に生産し，安定供給を実現する手法が盛んに研究されている。例えば，１５−ヒドロキシペンタデカン酸を加熱，重合させることにより，ポリエステルを生成させ，次いで触媒の存在下，このポリエステルを減圧下，過熱することにより解重合させ，シクロペンタデカノリドを得ることができる（特許文献１参照）。１５−ヒドロキシペンタデカン酸とグリセリンのエステルを触媒とともに減圧下で加熱することにより，シクロペンタデカノリドを得る方法も報告されている（特許文献２参照）。 Perfumes are added to cosmetics, cosmetics, foods, etc., and are frequently used to impart aroma and increase the added value of cosmetics, cosmetics, foods, etc. Among them, musk, which is known as one of natural fragrances, has been prized for a long time and is still in high demand. However, animals such as male musk deer, the source of musk, are in danger of extinction due to overfishing, and natural musk is difficult to obtain today. Musk aroma components are macrocyclic ketones such as muscone and civeton, and their analogs also have a musk-like aroma. In addition, (7Z) -ambridolide and cyclopentadecanolide, which are macrocyclic lactones obtained from the seeds of troiloeumodium and angelica, each have a musk-like aroma and are good substitutes for musk. However, the supply from plants is easily affected by the weather, etc., and varies greatly from year to year or season. Therefore, methods for artificially producing these macrocyclic lactones and achieving a stable supply are being actively studied. For example, 15-hydroxypentadecanoic acid can be heated and polymerized to form a polyester, and then depolymerized by heating the polyester under reduced pressure in the presence of a catalyst to obtain cyclopentadecanolide. (See Patent Document 1). A method for obtaining cyclopentadecanolide by heating an ester of 15-hydroxypentadecanoic acid and glycerin together with a catalyst under reduced pressure has also been reported (see Patent Document 2).
一方，（７Ｚ）−アンブレットリドの異性体である（９Ｅ）−イソアンブレットリドは天然には存在しないものの，ムスク様の香気を有する。そのため，人工香料としての用途が広く検討されており，その合成法も数多く報告されている。例えば，Ｍｏｏｋｈｅｒｊｅｅらは１，９−シクロヘキサデカジエンから酸化を経て誘導したヒドロキシシクロヘキサデカノンに対し，ＢＦ３・Ｅｔ２Ｏの存在下，過酸で処理することにより大環状ラクトン骨格を構築し，最後にパラ−トルエンスルホン酸で処理することにより，（９Ｅ）−イソアンブレットリドを得ている（特許文献３参照）。また，Ｂｈａｔｔａｃｈａｒｙｙａらはトレオ−アリューリット酸の水酸基を臭素に変換した後，エステル化，脱臭素化によるオレフィン形成，末端臭素のアセトキシル化，加水分解を経て得られる１６−ヒドロキシ−９−ヘキサデセン酸をトルエン中，加熱還流し，ポリマー化した後に解重合する方法を報告している（非特許文献４参照）。Ｔｓｅｎｇらはトレオ−アリューリット酸にオルトぎ酸トリメチルを反応させ，９，１０−位の水酸基を保護した後，無水酢酸と加熱することにより１６−アセトキシ−９−ヘキサデセン酸を合成し，次いで水酸化カリウムとグリセリンを混合，加熱することにより（９Ｅ）−イソアンブレットリドを得る方法を報告している（特許文献５参照）。この他にＶｉｌｌｅｍｉｎらにより，トレオ−アリューリット酸とジメチルホルムアミドジネオペンチルアセタールのトルエン溶液を不活性雰囲気下，加熱還流した後，トルエンを減圧蒸留で除き，次いで無水酢酸を加えた後，加熱還流することで（９Ｅ）−イソアンブレットリドを得る方法が報告されている（非特許文献６参照）。On the other hand, (9E) -isoambretlide, which is an isomer of (7Z) -ambretlide, does not exist in nature, but has a musk-like aroma. Therefore, its use as an artificial fragrance has been widely studied, and many synthetic methods have been reported. For example, Mookerjee et al. Constructed a macrocyclic lactone skeleton by treating hydroxycyclohexadecanone derived from 1,9-cyclohexadecadiene through oxidation with peracid in the presence of BF 3 · Et 2 O. Finally, (9E) -isoambulettelide is obtained by treatment with para-toluenesulfonic acid (see Patent Document 3). Bhattacharya et al. Also converted 16-hydroxy-9-hexadecenoic acid obtained by converting the hydroxyl group of threo-allitrit acid to bromine, followed by olefin formation by esterification and debromination, acetoxylation of terminal bromine, and hydrolysis. A method for depolymerization after heating to reflux in toluene and polymerizing has been reported (see Non-Patent Document 4). Tseng et al. Synthesizes 16-acetoxy-9-hexadecenoic acid by reacting threo-aluritic acid with trimethyl orthoformate, protecting the 9,10-hydroxyl group, and then heating with acetic anhydride, followed by water A method for obtaining (9E) -isoamburettolide by mixing and heating potassium oxide and glycerin has been reported (see Patent Document 5). In addition, according to Villemin et al., A toluene solution of threo-allylittic acid and dimethylformamide dineopentyl acetal was heated to reflux in an inert atmosphere, toluene was removed by distillation under reduced pressure, acetic anhydride was added, and then heated to reflux. Thus, a method for obtaining (9E) -isoambulettolide has been reported (see Non-Patent Document 6).
Ｍｏｏｋｈｅｒｊｅｅらの方法は１，９−シクロへキサデカジエンから（９Ｅ）−イソアンブレットリドを合成できるが，５工程と工程数が多く，また，二重結合部位の酸化工程における位置選択性が低いことや環拡大工程においても複数の位置異性体が生成し，それらの分離が困難であるなどの問題点が指摘されている。Ｂｈａｔｔａｃｈａｒｙｙａ，Ｔｓｅｎｇ，Ｖｉｌｌｅｍｉｎらの方法はいずれも短工程で（９Ｅ）−イソアンブレットリドが得られるが，環化反応を行う際に酸触媒による加熱脱水や減圧下での加熱縮合など過酷な条件が必要である。また，ポリマー化した後に再度脱ポリマー化を行うなど反応効率が低いなどの問題点を有しており，（９Ｅ）−イソアンブレットリドを効率よく得る方法とは言い難い。（９Ｅ）−イソアンブレットリドを含む不飽和大環状ラクトンをより温和な条件下で収率良く得るための方法が強く求められている。 The method of Mooherjee et al. Can synthesize (9E) -isoambretlide from 1,9-cyclohexadecadiene, but it has 5 steps and a large number of steps, and the regioselectivity in the oxidation step of the double bond site is low. Several problems have been pointed out, such as the formation of multiple positional isomers in the ring expansion process and the difficulty in separating them. Bhattacharya, Tseng, Villemin, etc. can all produce (9E) -isoambretlide in a short process, but severe conditions such as heat dehydration with acid catalyst and heat condensation under reduced pressure are required for the cyclization reaction. is required. In addition, it has problems such as low reaction efficiency such as depolymerization after polymerization, and it is difficult to say that it is a method for efficiently obtaining (9E) -isoambridolide. There is a strong demand for a method for obtaining an unsaturated macrocyclic lactone containing (9E) -isoambulettolide in a high yield under milder conditions.
そこで，発明者らは鋭意研究を重ね，本発明を完成するに至った。すなわち本発明は活性化剤および下記構造式 Thus, the inventors have conducted extensive research and have completed the present invention. That is, the present invention provides an activator and the following structural formula
本発明の代表的な例として，２−メチル−６−ニトロ安息香酸無水物を用いた（９Ｅ）−イソアンブレットリドの合成法を例示する。 As a representative example of the present invention, a method for synthesizing (9E) -isoambulettelide using 2-methyl-6-nitrobenzoic anhydride is illustrated.
第一工程はトレオ−アリューリット酸をラクトン化する工程である。活性化剤としてはピリジン，トリエチルアミン，Ｎ−メチルピペリジンのごとき有機塩基，及び４−ジメチルアミノピリジン（ＤＭＡＰ），４−ピロリジノピリジン（ＰＰＹ），４−ジメチルアミノピリジンＮ−オキシド（ＤＭＡＰＯ），４−ピロリジノピリジンＮ−オキシド（ＰＰＹＯ），塩基に不活性化されないルイス酸，遷移金属触媒などを単独，もしくは組み合わせて用いる。この反応で使用し得る溶媒はジクロロメタン，エチルエーテル，ＴＨＦ，アセトニトリル，ニトロメタン，トルエンなどが挙げられる。反応温度は０℃から溶媒の還流温度で適宜選択されるが，好ましくは２５℃である。反応時間は使用する活性化剤，溶媒により異なるが，６時間から２４時間で適宜選択される。 The first step is a step of lactonizing threo-aluritic acid. Activators include organic bases such as pyridine, triethylamine, N-methylpiperidine, and 4-dimethylaminopyridine (DMAP), 4-pyrrolidinopyridine (PPY), 4-dimethylaminopyridine N-oxide (DMAPO), 4 -Pyrrolidinopyridine N-oxide (PPYO), a Lewis acid not deactivated by a base, a transition metal catalyst or the like is used alone or in combination. Solvents that can be used in this reaction include dichloromethane, ethyl ether, THF, acetonitrile, nitromethane, toluene and the like. The reaction temperature is appropriately selected from 0 ° C. to the reflux temperature of the solvent, and preferably 25 ° C. The reaction time varies depending on the activator and solvent to be used, but is appropriately selected from 6 hours to 24 hours.
第二工程は得られたラクトンの水酸基に保護基を導入する工程である。保護剤としては１，１’−チオカルボニルジイミダゾールあるいはチオホスゲンを用いる。触媒としてはＤＭＡＰ，ＰＰＹ，ＤＭＡＰＯ，ＰＰＹＯなどを用いる。この反応で使用し得る溶媒はジクロロメタン，エチルエーテル，ＴＨＦ，アセトニトリル，ニトロメタン，トルエンなどが挙げられる。反応温度は−７８℃から溶媒の還流温度で適宜選択される。反応時間は使用する活性化剤，溶媒により異なるが，１時間から１２時間で適宜選択される。 The second step is a step of introducing a protecting group into the hydroxyl group of the obtained lactone. As the protective agent, 1,1'-thiocarbonyldiimidazole or thiophosgene is used. As the catalyst, DMAP, PPY, DMAPO, PPYO or the like is used. Solvents that can be used in this reaction include dichloromethane, ethyl ether, THF, acetonitrile, nitromethane, toluene and the like. The reaction temperature is appropriately selected from −78 ° C. to the reflux temperature of the solvent. The reaction time varies depending on the activator and solvent to be used, but is appropriately selected from 1 hour to 12 hours.
第三工程は脱酸素官能基化反応により二重結合を形成し，（９Ｅ）−イソアンブレットリドを得る工程である。脱酸素官能基化は亜りん酸エステル類中で行われる。反応温度は１０℃から２００℃の間で選択される。反応時間は１２時間から４８時間で適宜選択される。 The third step is a step of forming (9E) -isoambuletlide by forming a double bond by deoxygenation functionalization reaction. Deoxygenation functionalization takes place in phosphites. The reaction temperature is selected between 10 ° C and 200 ° C. The reaction time is appropriately selected from 12 hours to 48 hours.
以上のように本発明に係るラクトン製造法を用いることにより，効率的に不飽和大環状ラクトンを得ることができる。特にラクトン化の工程は縮合剤として安息香酸無水物を用いることにより，トリヒドロキシカルボン酸の中間位の水酸基を保護することなく，温和な条件下，直接ジヒドロキシラクトンを高収率で得るこをができる。従って，本発明は不飽和大環状ラクトンを得るための極めて有用な手段といえる。 As described above, an unsaturated macrocyclic lactone can be efficiently obtained by using the lactone production method according to the present invention. In particular, in the lactonization step, by using benzoic anhydride as a condensing agent, dihydroxylactone can be directly obtained in high yield under mild conditions without protecting the hydroxyl group at the intermediate position of trihydroxycarboxylic acid. it can. Therefore, the present invention can be said to be a very useful means for obtaining an unsaturated macrocyclic lactone.
以下に本発明の好ましい実施例を記載するが，これは例示の目的であり，本発明を制限するものではない。本発明の範囲内では変形が可能なことは当業者には明らかであろう。 In the following, preferred embodiments of the present invention will be described, but this is for illustrative purposes and is not intended to limit the present invention. It will be apparent to those skilled in the art that variations are possible within the scope of the invention.
トレオ−９，１０−ジヒドロキシヘプタデカン−１６−オリドの合成
２−メチル−６−ニトロ安息香酸無水物１６５ｍｇ（０．４７９ｍｍｏｌ），ＤＭＡＰＯ１１．１ｍｇ（０．０８０ｍｍｏｌ），トリエチルアミン８９．１ｍｇ（０．８８１ｍｍｏｌ）をジクロロメタン１６９ｍｌに溶解し，それに室温下，トレオ−アリューリット酸１１８ｍｇ（０．３８８ｍｍｏｌ）をＴＨＦ４０ｍｌに溶解したものをシリンジで１２時間かけて徐々に加えた。室温下，１時間攪拌した後，０℃で飽和炭酸水素ナトリウム水溶液を加えた。混合物にジクロロメタンを加え有機層を抽出した後，水及び食塩水で洗浄し，硫酸ナトリウムで乾燥した。ろ過した後，エバポレーターで溶媒を除去した。粗生物を薄層クロマトグラフィーで精製し，トレオ−９，１０−ジヒドロキシヘプタデカン−１６−オリドの白色固体を９２．０ｍｇ（収率８３％）得た。
以下に主な物性を示す。
融点：５３．５−５４．０℃
ＩＲ（ＫＢｒ）３４４０，３３１０，１７３０ｃｍ−１；１Ｈ ＮＭＲ（ＣＤＣｌ３）：δ４．１８−４．０５（ｍ，２Ｈ，１６−Ｈ），３．５０−３．４１（ｂｒ ｍ，２Ｈ，９−Ｈ，１０−Ｈ），２．４０（ｂｒｓ，２Ｈ，９−ＯＨ，１０−ＯＨ），２．３１（ｔ，Ｊ＝６．８Ｈｚ，２Ｈ，２−Ｈ），１．７０−１．２２（ｍ，２２Ｈ，３，４，５，６，７，８，１１，１２，１３，１４，１５−Ｈ）；１３Ｃ ＮＭＲ（ＣＤＣｌ３）：δ１７４．０（１），７４．１（９ｏｒ１０），７３．４（１０ｏｒ９），６４．２（１６），３４．６（２），３２．５，３１．４，２８．６，２８．２，２８．１，２７．７，２７．６，２５．４，２５．０，２３．９，２３．１（３，４，５，６，７，８，１１，１２，１３，１４，１５）；ＨＲ ＭＳ：ｃａｌｃｄ．ｆｏｒ Ｃ１６Ｈ３１Ｏ４（Ｍ＋Ｈ＋）２８７．２２２２，ｆｏｕｎｄ２８７．２２２３Synthesis of threo-9,10-dihydroxyheptadecan-16-orido 2-methyl-6-nitrobenzoic anhydride 165 mg (0.479 mmol), DMAPO 11.1 mg (0.080 mmol), triethylamine 89.1 mg (0.881 mmol) ) Was dissolved in 169 ml of dichloromethane, and at room temperature, 118 mg (0.388 mmol) of threo-allitrit acid dissolved in 40 ml of THF was gradually added by syringe over 12 hours. After stirring at room temperature for 1 hour, a saturated aqueous sodium hydrogen carbonate solution was added at 0 ° C. Dichloromethane was added to the mixture, and the organic layer was extracted, washed with water and brine, and dried over sodium sulfate. After filtration, the solvent was removed with an evaporator. The crude product was purified by thin layer chromatography to obtain 92.0 mg (83% yield) of a white solid of threo-9,10-dihydroxyheptadecan-16-orido.
The main physical properties are shown below.
Melting point: 53.5-54.0 ° C
IR (KBr) 3440, 3310, 1730 cm −1 ; 1 H NMR (CDCl 3 ): δ 4.18-4.05 (m, 2H, 16-H), 3.50-3.41 (br m, 2H, 9-H, 10-H), 2.40 (brs, 2H, 9-OH, 10-OH), 2.31 (t, J = 6.8 Hz, 2H, 2-H), 1.70-1. .22 (m, 22H, 3, 4, 5, 6, 7, 8, 11, 12, 13, 14 , 15-H); 13 C NMR (CDCl 3 ): δ 174.0 (1), 74.1 (9 or 10), 73.4 (10 or 9), 64.2 (16), 34.6 (2), 32.5, 31.4, 28.6, 28.2, 28.1, 27.7, 27 .6,25.4,25.0,23.9,23.1 (3,4,5,6,7,8,11,12,13,14,15); R MS: calcd. for C 16 H 31 O 4 (M + H + ) 287.2222, found 287.2223
トレオ−９，１０−チオカルボニルジオキシヘプタデカン−１６−オリドの合成
トレオ−９，１０−ジヒドロキシヘプタデカン−１６−オリド８０．２ｍｇ（０．２８０ｍｍｏｌ）をトルエン１４ｍｌに溶解し，それに１，１’−チオカルボニルジイミダゾール４９９ｍｇ（２．８０ｍｍｏｌ）とＤＭＡＰ３．４ｍｇ（０．０２８ｍｍｏｌ）を加えた。１３０℃で４時間攪拌した後，室温まで冷却した。エバポレーターで濃縮した後，薄層クロマトグラフィーで精製し，トレオ−９，１０−チオカルボニルジオキシヘプタデカン−１６−オリドの白色固体を８３．８ｍｇ（収率９１％）得た。
以下に主な物性を示す。
融点：７３−４°Ｃ
ＩＲ（ＫＢｒ）１７２０，１２８０，１１８０ｃｍ−１；１Ｈ ＮＭＲ（ＣＤＣｌ３）：δ４．５５−４．４３（ｍ，２Ｈ，９−Ｈ，１０−Ｈ），４．２１−４．０８（ｍ，２Ｈ，１６−Ｈ），２．４２−２．２５（ｍ，２Ｈ，２−Ｈ），２．１０−１．２１（ｍ，２２Ｈ，３，４，５，６，７，８，１１，１２，１３，１４，１５−Ｈ）；１３Ｃ ＮＭＲ（ＣＤＣｌ３）：δ１９１．４（ＣＳ），１７３．７（１），８６．１（９），８６．１（１０），６３．９（１６），３４．４（２），３２．４，３２．１，２８．７，２８．３，２７．９，２７．１，２５．６，２５．０，２３．６，２３．２（３，４，５，６，７，８，１１，１２，１３，１４，１５）；ＨＲ ＭＳ：ｃａｌｃｄ．ｆｏｒ Ｃ１７Ｈ２９Ｏ４Ｓ（Ｍ＋Ｈ＋）３２９．１７８６，ｆｏｕｎｄ３２９．１７９１Synthesis of threo-9,10-thiocarbonyldioxyheptadecan-16-olide 80.2 mg (0.280 mmol) of threo-9,10-dihydroxyheptadecane-16-olide was dissolved in 14 ml of toluene, and 1,1 499 mg (2.80 mmol) of '-thiocarbonyldiimidazole and 3.4 mg (0.028 mmol) of DMAP were added. After stirring at 130 ° C. for 4 hours, the mixture was cooled to room temperature. After concentration with an evaporator, purification was performed by thin layer chromatography to obtain 83.8 mg (yield 91%) of a white solid of threo-9,10-thiocarbonyldioxyheptadecan-16-orido.
The main physical properties are shown below.
Melting point: 73-4 ° C
IR (KBr) 1720, 1280, 1180 cm −1 ; 1 H NMR (CDCl 3 ): δ 4.55-4.43 (m, 2H, 9-H, 10-H), 4.21-4.08 (m , 2H, 16-H), 2.42-2.25 (m, 2H, 2-H), 2.10-1.21 (m, 22H, 3, 4, 5, 6, 7, 8, 11 , 12, 13, 14, 15-H); 13 C NMR (CDCl 3 ): δ 191.4 (CS), 173.7 (1), 86.1 (9), 86.1 (10), 63. 9 (16), 34.4 (2), 32.4, 32.1, 28.7, 28.3, 27.9, 27.1, 25.6, 25.0, 23.6, 23. 2 (3,4,5,6,7,8,11,12,13,14,15); HR MS: calcd. for C 17 H 29 O 4 S (M + H + ) 329.1786, found 329.1791
（９Ｅ）−イソアンブレットリドの合成
トレオ−９，１０−チオカルボニルジオキシヘプタデカン−１６−オリド２０．４ｍｇ（０．０６２ｍｍｏｌ）を室温下，亜りん酸トリメチル３ｍｌに溶解し，１４０℃で２５時間攪拌した後，室温まで冷却した。エバポレーターで濃縮した後，薄層クロマトグラフィーで精製し，（９Ｅ）−イソアンブレットリドの無色透明油状液体を１３．７ｍｇ（収率８７％）得た。
以下に主な物性を示す。
ＩＲ（ｎｅａｔ）１７３０ｃｍ−１；１Ｈ ＮＭＲ（Ｃ６Ｄ６）：δ５．４２（ｄｄｄｄ，Ｊ＝１５４．９．５，３．５，１．６Ｈｚ，１Ｈ，９−Ｈｏｒ１０−Ｈ），５．３２（ｄｄｄｄ，Ｊ＝１５．４，９．５，３．８，１．６Ｈｚ，１Ｈ，１０−Ｈｏｒ９−Ｈ），４．０８（ｔ，Ｊ＝５．４Ｈｚ，２Ｈ，１６−Ｈ），２．１９（ｔ，Ｊ＝７．０Ｈｚ，２Ｈ，２−Ｈ），２．１２−１．９７（ｍ，４Ｈ，８−Ｈ，１１−Ｈ），１．６２−１．５０（ｍ，２Ｈ，３−Ｈ），１．４８−１．３４（ｍ，２Ｈ，１５−Ｈ），１．４２−１．１３（ｍ，１４Ｈ，４，５，６，７，１２，１３，１４−Ｈ）；１３Ｃ ＮＭＲ（Ｃ６Ｄ６）：δ１７２．９（１），１３１．４（９ｏｒ１０），１３０．８（１０ｏｒ９），６４．０（１６），３４．９（２），３２．２（８ｏｒ１１），３１．８（１１ｏｒ８），２９．２（１５），２９．９，２８．８，２８．３，２８．２，２８．１，２７．２，２７．１（４，５，６，７，１２，１３，１４），２５．３（３）；ＨＲ ＭＳ：ｃａｌｃｄ．ｆｏｒ Ｃ１６Ｈ２９Ｏ２（Ｍ＋Ｈ＋）２５３．２１６７，ｆｏｕｎｄ２５３．２１６５Synthesis of (9E) -isoambulettolide 20.4 mg (0.062 mmol) of threo-9,10-thiocarbonyldioxyheptadecane-16-olide was dissolved in 3 ml of trimethyl phosphite at room temperature, at 140 ° C. After stirring for 25 hours, it was cooled to room temperature. After concentrating with an evaporator, it was purified by thin layer chromatography to obtain 13.7 mg (yield 87%) of a colorless transparent oily liquid of (9E) -isoambulettolide.
The main physical properties are shown below.
IR (neat) 1730 cm −1 ; 1 H NMR (C 6 D 6 ): δ 5.42 (dddd, J = 154.9.5, 3.5, 1.6 Hz, 1H, 9-Hor10-H), 5 .32 (dddd, J = 15.4, 9.5, 3.8, 1.6 Hz, 1H, 10-Hor9-H), 4.08 (t, J = 5.4 Hz, 2H, 16-H) , 2.19 (t, J = 7.0 Hz, 2H, 2-H), 2.12-1.97 (m, 4H, 8-H, 11-H), 1.62-1.50 (m , 2H, 3-H), 1.48-1.34 (m, 2H, 15-H), 1.42-1.13 (m, 14H, 4, 5, 6, 7, 12, 13, 14 -H); 13 C NMR (C 6 D 6): δ172.9 (1), 131.4 (9or10), 130.8 (10or9), 64.0 (16), 34 9 (2), 32.2 (8or11), 31.8 (11or8), 29.2 (15), 29.9, 28.8, 28.3, 28.2, 28.1, 27.2 27.1 (4, 5, 6, 7, 12, 13, 14), 25.3 (3); HR MS: calcd. for C 16 H 29 O 2 (M + H + ) 253.2167, found 253.2165
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