JP2011162506A - エピガロカテキンガレート誘導体及びそれを含む医薬組成物 - Google Patents

エピガロカテキンガレート誘導体及びそれを含む医薬組成物 Download PDF

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JP2011162506A
JP2011162506A JP2010028974A JP2010028974A JP2011162506A JP 2011162506 A JP2011162506 A JP 2011162506A JP 2010028974 A JP2010028974 A JP 2010028974A JP 2010028974 A JP2010028974 A JP 2010028974A JP 2011162506 A JP2011162506 A JP 2011162506A
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Takashi Takahashi
孝志 高橋
Hiroshi Tanaka
浩士 田中
Hirofumi Tachibana
宏文 立花
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Kyushu University NUC
Tokyo Institute of Technology NUC
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Abstract

【課題】エピガロカテキンガレートのヒドロキシ基の一部がメトキシ基に置換されており、エピガロカテキンガレートと同等又はそれ以上の抗腫瘍活性又は抗アレルギー活性を持つ誘導体の提供。
【解決手段】一般式（Ｉ）
Figure 2011162506

〔式中、Ｘは疎水性基を表し、Ｒ１及びＲ２は同一又は異なって、置換基を有していてもよいフェニル基を表す。〕で表される化合物。
【選択図】なし

Description

本発明は、新規なエピガロカテキンガレート誘導体及びそれを含む医薬組成物に関する。
エピガロカテキンガレートは、in vitro の評価系において抗腫瘍作用や抗アレルギー作用などの様々な作用を有するが明らかになっているが、体内動態はよくないことが知られている。
エピガロカテキンガレートのヒドロキシ基の一部がメトキシ基に置換された誘導体は、体内動態の向上が期待できる。エピガロカテキンガレートのD 環部のヒドロキシ基の一部がメトキシ基に置換された誘導体は、in vivo で抗アレルギー作用を示すことが明らかにされており（非特許文献１、非特許文献２、非特許文献３）、そのようなエピガロカテキンガレート誘導体を含む「べにふうき」は、アレルギー症状を抑える効果があることが証明されている。しかし、そのような誘導体は、in
vitro 評価系では、オリジナルのエピガロカテキンガレートよりも活性が低下することが明らかにされている（非特許文献４）。
J. Agric. Food Chem. 2002, 50,5729-5734 5729 The Journal of Immunology, 2004,172: 4486-4492. Biochemical and Biophysical ResearchCommunications 364 (2007) 79-85 J. Agric. Food Chem. 2007, 55,7144-7148
上述したように、エピガロカテキンガレートのヒドロキシ基の一部をメトキシ基に置換した誘導体は、体内動態が向上するもののエピガロカテキンガレートよりも活性が低下してしまう。
本発明は、以上のような技術的背景の下になされたものであり、エピガロカテキンガレートのヒドロキシ基の一部がメトキシ基に置換されているが、エピガロカテキンガレートと同等又はそれ以上の抗腫瘍活性又は抗アレルギー活性を持つ誘導体を提供することを目的とする。
本発明者は、上記課題を解決するため鋭意検討を重ねた結果、エピガロカテキンガレートのＡ環の７位のヒドロキシ基をメトキシ基に置換しても、エピガロカテキンガレートの抗腫瘍活性は低下せず、むしろ向上することを見出した。その一方、Ａ環の５位のヒドロキシ基をメトキシ基に置換すると、抗腫瘍活性が低下することが多いことも見出した。
本発明は、以上の知見に基づき完成されたものである。
即ち、本発明は、以下の（１）〜（９）を提供する。
（１）一般式（Ｉ）
Figure 2011162506
 〔式中、Ｘは疎水性基を表し、Ｒ１及びＲ２は同一又は異なって、置換基を有していてもよいフェニル基を表す。〕
で表される化合物。
（２）一般式（Ｉ）におけるＸが、１〜６個の不飽和結合を含んでもよく、また、酸素原子又は窒素原子を含んでもよい直鎖状又は分岐鎖状の炭化水素基であることを特徴とする（１）に記載の化合物。
（３）一般式（Ｉ）におけるＸが、置換基を有していてもよいアルキル基、置換基を有していてもよいアルケニル基、置換基を有していてもよいアルキニル基、置換基を有していてもよいアルコキシ基、置換基を有していてもよいアルケニルオキシ基、置換基を有していてもよいアルキニルオキシ基、置換基を有していてもよいアルコキシアルコキシ基、置換基を有していてもよいアルコキシアルコキシアルコキシ基、ハロゲン原子、又は水素原子であることを特徴とする（１）に記載の化合物。
（４）一般式（Ｉ）におけるＸが、メトキシ基又はエトキシ基であることを特徴とする（１）に記載の化合物。
（５）一般式（Ｉ）におけるＲ１及びＲ２が、同一又は異なって、ヒドロキシ基及び／又はメトキシ基を有するフェニル基であることを特徴とする（１）乃至（４）のいずれかに記載の化合物。
（６）一般式（Ｉ）におけるＲ１及びＲ２が、同一又は異なって、3,4,5-トリメトキシフェニル基、4-ヒドロキシ-3,5-ジメトキシフェニル基、3,5-ジヒドロキシ-4-メトキシフェニル基、又は3,4,5-トリヒドロキシフェニル基であることを特徴とする（１）乃至（４）のいずれかに記載の化合物。
（７）（１）乃至（６）のいずれかに記載の化合物を含有することを特徴とする医薬組成物。
（８）（１）乃至（６）のいずれかに記載の化合物を含有することを特徴とする抗腫瘍剤。
（９）（１）乃至（６）のいずれかに記載の化合物を含有することを特徴とする抗アレルギー剤。
本発明のエピガロカテキンガレート誘導体は、高い抗腫瘍作用や抗アレルギー作用を持つので、抗腫瘍剤や抗アレルギー剤などの医薬成分として有用である。
実施例１で合成したエピガロカテキンガレート誘導体の構造式を示す図。 各エピガロカテキンガレート誘導体の細胞増殖抑制活性を示す図。図中に記載されているグラフの番号は、図１中に記載されている化合物の番号と対応する。
以下、本発明を詳細に説明する。
本発明において「アルキル基」とは、例えば、炭素数１〜４０のアルキル基であり、好適には、炭素数１〜１０のアルキル基である。アルキル基は、直鎖状及び分岐鎖状のいずれであってもよい。また、「置換基を有していてもよいアルキル基」とは、置換可能な位置に１若しくは２以上の置換基を有していてもよいアルキル基を意味する。置換基としては、ハロゲン原子、アジド基、アセトアミド基などを例示できる。
本発明において「アルケニル基」とは、例えば、炭素数２〜４０のアルケニル基であり、好適には、炭素数２〜１０のアルケニル基である。アルケニル基は、直鎖状及び分岐鎖状のいずれであってもよい。「アルケニル基」には、プレニル基も含まれる。プレニル基としては、ジメチルアリル基、ゲラニル基、ファルネシル基、ゲラニルゲラニル基などが含まれる。また、「置換基を有していてもよいアルケニル基」とは、置換可能な位置に１若しくは２以上の置換基を有していてもよいアルケニル基を意味する。置換基としては、ハロゲン原子、アジド基、アセトアミド基などを例示できる。
本発明において「アルキニル基」とは、例えば、炭素数２〜４０のアルキニル基であり、好適には、炭素数２〜１０のアルキニル基である。アルキニル基は、直鎖状及び分岐鎖状のいずれであってもよい。また、「置換基を有していてもよいアルキニル基」とは、置換可能な位置に１若しくは２以上の置換基を有していてもよいアルキニル基を意味する。置換基としては、ハロゲン原子、アジド基、アセトアミド基などを例示できる。
本発明において「アルコキシ基」とは、例えば、炭素数１〜４０のアルコキシ基であり、好適には、炭素数１〜１５のアルコキシ基である。アルコキシ基は、直鎖状及び分岐鎖状のいずれであってもよい。また、「置換基を有していてもよいアルコキシ基」とは、置換可能な位置に１若しくは２以上の置換基を有していてもよいアルコキシ基を意味する。置換基としては、ハロゲン原子、アジド基、アセトアミド基などを例示できる。
本発明において「アルケニルオキシ基」とは、例えば、炭素数２〜４０のアルケニルオキシ基であり、好適には、炭素数２〜１５のアルケニルオキシ基である。アルケニルオキシ基は、直鎖状及び分岐鎖状のいずれであってもよい。「アルケニルオキシ基」には、プレニルオキシ基も含まれる。プレニルオキシ基としては、ジメチルアリルオキシ基、ゲラニルオキシ基、ファルネシルオキシ基、ゲラニルゲラニルオキシ基などが含まれる。
本発明において「アルキニルオキシ基」とは、例えば、炭素数２〜４０のアルキニルオキシ基であり、好適には、炭素数２〜１５のアルキニルオキシ基である。アルキニルオキシ基は、直鎖状及び分岐鎖状のいずれであってもよい。また、「置換基を有していてもよいアルキニルオキシ基」とは、置換可能な位置に１若しくは２以上の置換基を有していてもよいアルキニルオキシ基を意味する。置換基としては、ハロゲン原子、アジド基、アセトアミド基などを例示できる。
本発明において「アルコキシアルコキシ基」とは、例えば、炭素数２〜８０のアルコキシアルコキシ基であり、好適には、炭素数２〜３０のアルコキシアルコキシ基である。アルコキシアルコキシ基は、直鎖状及び分岐鎖状のいずれであってもよい。また、「置換基を有していてもよいアルコキシアルコキシ基」とは、置換可能な位置に１若しくは２以上の置換基を有していてもよいアルコキシアルコキシ基を意味する。置換基としては、ハロゲン原子、アジド基、アセトアミド基などを例示できる。置換基を有するアルコキシアルコキシ基の具体例としては、２−（２−クロロエトキシ）エトキシ基、２−（２−アジドエトキシ）エトキシ基、２−（２−アセトアミドエトキシ）エトキシ基などを挙げることができる。
本発明において「アルコキシアルコキシアルコキシ基」とは、例えば、炭素数３〜１２０のアルコキシアルコキシアルコキシ基であり、好適には、炭素数３〜４５のアルコキシアルコキシアルコキシ基である。アルコキシアルコキシアルコキシ基は、直鎖状及び分岐鎖状のいずれであってもよい。また、「置換基を有していてもよいアルコキシアルコキシアルコキシ基」とは、置換可能な位置に１若しくは２以上の置換基を有していてもよいアルコキシアルコキシアルコキシ基を意味する。置換基としては、ハロゲン原子、アジド基、アセトアミド基などを例示できる。
本発明の化合物は、下記の一般式（Ｉ）
Figure 2011162506
 〔式中、Ｘは疎水性基を表し、Ｒ１及びＲ２は同一又は異なって、置換基を有していてもよいフェニル基を表す。〕
で表される。
一般式（Ｉ）においてＸは、好適には、１〜６個の不飽和結合を含んでもよく、また、酸素原子又は窒素原子を含んでもよい直鎖状又は分岐鎖状の炭化水素基であり、より好適には、置換基を有していてもよいアルキル基、置換基を有していてもよいアルケニル基、置換基を有していてもよいアルキニル基、置換基を有していてもよいアルコキシ基、置換基を有していてもよいアルケニルオキシ基、置換基を有していてもよいアルキニルオキシ基、置換基を有していてもよいアルコキシアルコキシ基、置換基を有していてもよいアルコキシアルコキシアルコキシ基、ハロゲン原子、又は水素原子であり、更に好適には、メトキシ基又はエトキシ基であり、更に好適には、メトキシ基である。
一般式（Ｉ）においてＲ１は、好適には、ヒドロキシ基及び／又はメトキシ基を有するフェニル基であり、より好適には、3,4,5-トリメトキシフェニル基、4-ヒドロキシ-3,5-ジメトキシフェニル基、3,5-ジヒドロキシ-4-メトキシフェニル基、又は3,4,5-トリヒドロキシフェニル基である。
一般式（Ｉ）においてＲ２は、好適には、ヒドロキシ基及び／又はメトキシ基を有するフェニル基であり、より好適には、3,4,5-トリメトキシフェニル基、4-ヒドロキシ-3,5-ジメトキシフェニル基、3,5-ジヒドロキシ-4-メトキシフェニル基、又は3,4,5-トリヒドロキシフェニル基である。
一般式（Ｉ）で表される化合物のうち代表的なものとしては、図１中の番号３３〜４８で示される化合物を例示できる。これらの化合物の中でも番号４３〜４８で示される化合物が好ましく、番号３３〜４２で示される化合物がより好ましい。
一般式（Ｉ）で表される化合物は、実施例に記載されている方法に従って合成することができる。例えば、１）ベンズアルデヒド誘導体を担体に固定する、２）ベンズアルデヒド誘導体とアセトフェノン誘導体を反応させる、３）反応性生物をエポキシ化した後、エポキシを開環させる、４）安息香酸誘導体によってエステル化する、５）担体から切り出す、５）脱保護する、ことによって、一般式（Ｉ）で表される化合物を合成できる。
実施例で示されているように、一般式（Ｉ）で表される化合物は、高い抗腫瘍作用を有する。また、エピガロカテキンガレートの抗腫瘍作用も抗アレルギー作用も67kDaラミニンレセプター(67LR)を介して発揮されるので（抗腫瘍に関する文献：THE JOURNAL OF BIOLOGICAL
CHEMISTRY VOL. 283, NO. 6, pp. 3050-3058, February 8, 2008、Biochemical and
Biophysical Research Communications 371 (2008) 172-176、Biochemical and
Biophysical Research Communications 333 (2005) 628-635、Blood.
2006;108:2804-2810、British Journal of Haematology
doi:10.1111/j.1365-2141.2009.08040、抗アレルギー作用に関する文献：Biochemical and Biophysical
Research Communications 364 (2007) 79-85、Biochemical and Biophysical Research
Communications 336 (2005) 674-681、Biochemical and Biophysical Research
Communications 348 (2006) 524-531、Archives of Biochemistry and Biophysics 476
(2008) 133-138）、一般式（Ｉ）で表される化合物は、抗アレルギー作用についても高い活性を持つと考えられる。このように一般式（Ｉ）で表される化合物は、抗腫瘍作用と抗アレルギー作用を持つことから、医薬組成物、抗腫瘍剤、抗アレルギー剤などの用途に利用できる。
本発明の医薬組成物、抗腫瘍剤、及び抗アレルギー剤（以下、「本発明の医薬組成物等」という）は、有効成分である一般式（Ｉ）で表される化合物の他、賦形剤、安定剤、湿潤剤、乳化剤、吸収促進剤、ｐＨ調整剤、界面活性剤、稀釈剤、担体、溶解助剤、矯味剤、保存剤、芳香剤、着色剤、コーティング剤などの添加成分や水などを含むものであってもよい。
本発明の医薬組成物等は、経口投与、非経口投与いずれの投与方法をも採用することができ、それぞれに適した医薬製剤の形態とすることができる。医薬製剤としては、例えば、液剤、シロップ剤、注射剤、液状吸入剤、乳剤等の液状剤、錠剤、粉剤、顆粒剤、カプセル剤、軟膏剤、固形吸入剤、座剤等の固形剤などを挙げることができる。
本発明の医薬組成物等中の一般式（Ｉ）で表される化合物の含有量は、用途、剤型、配合目的等によって異なるが、一般的には、組成物全量中1〜100質量％が好ましく、より好ましくは10〜50質量％である。
本発明の医薬組成物等の投与量は、投与対象者の年齢、体重、投与方法などに応じて適宜決めればよい。例えば、通常成人１日当たり一般式（Ｉ）で表される化合物10〜1000mg、好ましくは、10〜100mgを１日１回又は数回に分けて投与することができる。
以下、実施例により本発明を更に詳細に説明する。
〔実施例１〕エピガロカテキンガレート誘導体の合成
（１）実験方法
（１−１）ベンズアルデヒドの固定化
６４個のMinKansTMにPS-Wang-Br レジン（ノバビオケム製）をそれぞれ７０mg程度とそれぞれを区別できるRFタグを入れた。そのMinKansTMを１６個づつ４つの反応容器に入れた。それぞれの反応容器に、対応するベンズアルデヒド（0.2 M）（３-ブロモ-２-ヒドロキシ-４、５-ジメトキシベンズアルデヒド、３-ブロモ-２-ヒドロキシ-４、５-ジ-p-フルロロベンジルオキシベンズアルデヒド、４-ベンジルオキシ-３-ブロモ-２-ヒドロキシ-５-メトキシベンズアルデヒド、５-ベンジルオキシ-３-ブロモ-２-ヒドロキシ-４-メトキシベンズアルデヒド）と炭酸セシウム（0.2 M）とヨウ化ナトリウム（0.06 M）のジメチルホルムアミド懸濁液の中で、２４時間、室温下撹拌した。反応後、すべてのMinKansTMをジメチルホルムアミド溶媒での１０分間の洗浄を３回、ジメチルホルムアミドと水（２：１）の混合溶液で１０分間の洗浄を３回、メタノールでの１０分間の洗浄を３回、ジクロロメタンでの１０分間の洗浄を３回行った後、レジンを減圧下乾燥させた。
Figure 2011162506
 （１−２）アルドール反応
同一のアルデヒドが固定化されたレジンを含むMinKansTM４個を一組とした４種類のアルデヒドが固定化されたレジン含むMinKansTM１６個を４種類の反応容器に入れた。それぞれの反応容器に対応するケトン（３、４、５-トリメトキシアセトフェノン、４-ベンジルオキシ-３、５-ジメトキシアセトフェノン、３、５-ジベンジルオキシ-４-メトキシアセトフェノン、３、４、５-トリベンジルオキシアセトフェノン）のテトラヒドロピラン溶液を入れた。さらに、０．１ Mナトリウムメトキシドのメタノール溶液を加え、室温下、２４時間反応させた。反応後、すべてのMinKansTMをテトラヒドロピラン溶媒で１０分間の洗浄を３回、テトラヒドロピランと水（２：１）の混合溶液で１０分間の洗浄を３回、ジメチルホルムアミド溶媒での１０分間の洗浄を３回、ジクロロメタンでの１０分間の洗浄を３回、メタノールでの１０分間の洗浄を３回行った後、レジンを減圧下乾燥させた。
Figure 2011162506
 （１−３）エポキシ化
６４個すべてのMinKansTMを同一の反応容器に入れた。その反応容器に、５．５ Mのtert-ブチルヒドロペルオキシドのデカン溶液と２．５ Ｍの水酸化カリウム水溶液を加え、室温下７２時間反応させた。反応後、すべてのMinKansTMをジクロロメタンでの１０分間の洗浄を３回、メタノールでの１０分間の洗浄を３回行った後、レジンを減圧下乾燥させた。
Figure 2011162506
 （１−４）エポキシの開環
６４個すべてのMinKansTMを同一の反応容器に入れた。その反応容器に、乾燥塩化メチレンとメタノール（１：１）の混合溶媒を加えた。さらに、０．０１Mのスカンジウムトリフレートを加え、室温下３時間反応させた後、トリエチルアミンを加えて反応を停止させた。その後、すべてのMinKansTMをアセトニトリルでの１０分間の洗浄を３回、ジクロロメタンでの１０分間の洗浄を３回、メタノールでの１０分間の洗浄を３回行った後、レジンを減圧下乾燥させた。
Figure 2011162506
 （１−５）エステル化
異なるアルデヒドとケトンを反応させたレジン含むMinKansTM１６個を一つの反応容器に入れた。それぞれの反応容器に、それぞれ対応するカルボン酸（３、４、５-トリメトキシ安息香酸、４-ベンジルオキシ-３、５-ジメトキシ安息香酸、３、５-ジベンジルオキシ-４-メトキシ安息香酸、３、４、５-トリベンジルオキシ安息香酸）とジクロロメタンとジメチルホルムアミド（１：４）の混合溶媒を加えた。さらに、０．２Mジイソプピルカルボジイミドと０．０６Mジメチルアミノピリジンを加え、室温下、４８時間反応させた。得られたすべてのMinKansTMをジメチルホルムアミド溶媒での１０分間の洗浄を３回、ジメチルホルムアミドと水（２：１）の混合溶液で１０分間の洗浄を３回、ジクロロメタンでの１０分間の洗浄を３回、メタノールでの１０分間の洗浄を３回行った後、レジンを減圧下乾燥させた。
Figure 2011162506
 （１−６）切り出し
６４個すべてのMinKansTMを別々の反応容器に入れて５％トリフルオロ酢酸の１０％トリエチルシランの塩化メチレン溶液を加えて、０度で８時間反応させた。MinKansTMをろ別後、酢酸エチルで薄めた後、濃縮した。得られた残査をシリカゲルカラムクロマトグラフィーにて精製することにより、６４種類のエピガロカテキンガレート誘導体の保護体を得た。
Figure 2011162506
 （１−７）脱保護
脱保護はTHALESNano社製のH-CubeTMを用いて行った。触媒カートリッジとして水酸化パラジウムのカートリッジを用いた。保護体のメタノールトテトラヒドロピラン（１：１）混合溶液に１％蟻酸を添加した。保護体 1mg/mLの溶液を調製した。水素圧（20bar）室温の反応条件に対して、その溶液を1mL/minの流速で流すことに寄って脱保護を行った。
Figure 2011162506
 （２）実験結果
（２−１）NMRデータ
合成した６４種類のエピガロカテキンガレート誘導体（脱保護体及び保護体）のNMRデータを以下に示す。

(±)-Epigallocatechin-3-gallate
(1)
TLC Rf 0.58 (methanol/H2O = 2/1,
reverse-phase); 1H NMR (400 MHz, acetone-d6/D2O = 2/1) δ 6.89 (s, 2H), 6.53 (s, 2H), 5.91 (d, J = 1.9 Hz, 1H), 5.89
(d, J = 1.9 Hz, 1H), 5.29 (br s, 1H), 4.90 (s, 1H), 2.83 (dd, Jgem = 17.4 Hz, J
= 4.4 Hz, 1H), 2.72 (d, Jgem = 17.4 Hz, 1H); 13C NMR (100 MHz, acetone-d6/D2O = 2/1)
δ 167.3, 157.0, 156.9, 146.0, 145.7, 139.3, 133.0, 130.6, 121.0, 110.2, 106.8,
99.0 96.5, 95.8, 77.9, 70.3, 26.4; FT-IR (solid) 3308, 1608, 1511, 1445, 1307,
1146, 1100, 1034, 914, 734, 644, 500 cm-1; HRMS (ESI-TOF) calcd for
C22H18O11 [M+H]+ 459.0969, found 459.0969.
4”-O-Methyl-epigallocatechin-3-gallate (2)
Yield 49%; TLC Rf 0.37 (CHCl3/methanol = 2/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) d 6.93 (s, 2H), 6.59
(s, 2H), 5.97 (d, J = 2.4 Hz, 1H), 5.95 (d, J = 1.9 Hz, 1H), 5.39 (br s, 1H),
4.97 (s, 1H), 3.72 (s, 3H), 2.95 (dd, Jgem = 17.4 Hz, J = 4.3 Hz, 1H), 2.84 (d,
Jgem = 17.4 Hz, 1H); FT-IR (solid) 1693, 1603, 1522, 1451, 1345, 1234, 1142,
1092, 1038, 882, 727, 636, 492 cm-1; HRMS (ESITOF) calcd for C23H21O11
[M+H]+ 473.1084, found 473.1088.
3”,4”-O-Dimethyl-epigallocatechin-3-gallate (3)
Yield 60%; TLC Rf 0.49 (CHCl3/methanol = 2/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.00 (d, J = 1.9 Hz, 1H), 6.91 (d, J = 1.9 Hz, 1H), 6.57 (s, 2H), 5.95 (d, J =
1.9 Hz, 1H), 5.94 (d, J = 1.9 Hz, 1H), 5.37 (br s, 1H), 4.98 (s, 1H), 3.73 (s,
3H), 3.68 (s, 3H), 2.94 (dd, Jgem = 17.4 Hz, J = 4.3 Hz, 1H), 2.85 (dd, Jgem =
17.4 Hz, J = 1.4 Hz, 1H); FT-IR (solid) 3282, 1696, 1603, 1607, 1510, 1455,
1340, 1226, 1146, 1112, 824, 803, 755, 645, 533 cm-1; HRMS (ESI-TOF)
calcd for C24H23O11 [M+H]+ 487.1240, found
487.1244.
3”,5”-O-Dimethyl-epigallocatechin-3-gallate (4)
Yield 35%; TLC Rf 0.49 (CHCl3/methanol
= 2/1); 1H NMR (400 MHz, acetone-d6/D2O = 2/1)
δ 7.07 (s, 2H), 6.59 (s, 2H), 5.96 (s, 1H), 5.96 (s, 1H), 5.35 (br s, 1H), 5.01
(s, 1H), 3.74 (s, 6H), 2.94 (d, Jgem = 18.4 Hz, 1H), 2.72 (d, Jgem = 18.4 Hz,
1H); FT-IR (solid) 3357, 1611, 1510, 1456, 1339, 1146, 1003, 803, 755, 646, 524
cm-1; HRMS (ESI-TOF) calcd for C24H23O11
[M+H]+ 487.1240, found 487.1239.
4’-O-Methyl-epigallocatechin-3-gallate (5)
Yield 68%; TLC Rf 0.43 (CHCl3/methanol = 2/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.97 (s, 2H), 6.61 (s, 2H), 5.99 (d, J = 2.4 Hz, 1H), 5.96 (d, J = 2.4 Hz, 1H),
5.40 (br s, 1H), 4.99 (s, 1H), 3.67 (s, 3H), 2.95 (dd, Jgem = 17.9 Hz, J = 4.4
Hz, 1H), 2.86 (d, Jgem = 17.9 Hz, 1H); FT-IR (solid) 3299, 1689, 1605, 1529,
1506, 1441, 1315, 1233, 1195, 1143, 1116, 1029, 1007, 820, 766, 628 cm-1;
HRMS (ESI-TOF) calcd for C23H21O11 [M+H]+
473.1084, found 473.1064.
4’,4”-O-Dimethyl-epigallocatechin-3-gallate(6)
Yield 63%; TLC Rf 0.32 (CHCl3/methanol = 3/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) d 6.89 (s, 2H, a),
6.59 (s, 2H, b), 5.95 (d, J = 2.4 Hz, 1H, c or d), 5.94 (d, J = 2.4 Hz, 1H, c
or d), 5.39 (br s, 1H, e), 4.98 (s, 1H, f), 3.70 (s, 3H, g or h), 3.64 (s, 3H,
g or h), 2.94 (dd, Jgem = 17.9 Hz, J = 4.8 Hz, 1H, i), 2.82 (dd, Jgem = 17.9
Hz, J = 1.9 Hz, 1H, i) FT-IR (solid) 3283, 1693, 1601, 1600, 1510, 1435, 1372,
1193, 1145, 1050, 986, 823, 755, 713, 540 cm-1; HRMS (ESI-TOF) calcd for C24H23O11
[M+H]+ 487.1240, found 487.1238.
4’,3”,4”-O-Trimethyl-epigallocatechin-3-gallate (7)
Yield 51%; TLC Rf 0.41 (CHCl3/methanol = 3/1); 1H NMR (400
MHz, acetone-d6/D2O = 2/1) d 7.00 (d, J = 1.9 Hz, 1H, a),
6.91 (d, J = 1.9 Hz, 1H, a), 6.58 (s, 2H, b), 5.95 (d, J = 2.4 Hz, 1H, c or d),
5.93 (d, J = 2.4 Hz, 1H, c or d), 5.39 (br s, 1H, e), 5.00 (s, 1H, f), 3.72 (s,
3H, g, h or i), 3.67 (s, 3H, g, h or i), 3.63 (s, 3H, g, h or i), 2.94 (dd, Jgem
= 17.4 Hz, J = 4.3 Hz, 1H, j), 2.87 (dd, Jgem = 17.4 Hz, J = 1.9 Hz, 1H, j);
FT-IR (solid) 3283, 1697, 1599, 1509, 1462, 1434, 1366, 1225, 1146, 1099, 1049,
1016, 1003, 824, 755, 714, 548 cm-1; HRMS (ESI-TOF) calcd for C25H25O11
[M+H]+ 501.1397, found 501.1390.
4’,3”,5”-O-Trimethyl-epigallocatechin-3-gallate (8)
Yield 34%; TLC Rf 0.41 (CHCl3/methanol = 3/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.05 (s, 2H), 6.61 (s, 2H), 5.96 (s, 1H), 5.96 (s, 1H), 5.37 (br s, 1H), 5.04
(s, 1H), 3.74 (s, 6H), 3.64 (s, 3H), 2.98 (dd, Jgem = 18.4 Hz, J = 4.4 Hz, 1H),
2.84 (dd, Jgem = 17.9 Hz, J = 2.9 Hz, 1H); FT-IR (solid) 3387, 1669, 1629,
1515, 1462, 1365, 1207, 1144, 1118, 1044, 960, 803, 755, 606 cm-1;
HRMS (ESI-TOF) calcd for C25H25O11
[M+H]+501.1397, found 501.1400
3’,5’-O-Dimethyl-epigallocatechin-3-gallate (9)
Yield 43%; TLC Rf 0.38 (CHCl3/methanol = 3/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) d 6.95 (s, 2H), 6.90
(s, 2H), 5.98 (d, J = 2.4 Hz, 1H), 5.96 (d, J = 2.4 Hz, 1H), 5.43 (br s, 1H),
5.05 (s, 1H), 3.64 (s, 6H), 2.96 (dd, Jgem = 17.4 Hz, J = 4.3 Hz, 1H), 2.81 (d,
Jgem = 17.4 Hz, 1H); FT-IR (solid) 3301, 1689, 1612, 1517, 1462, 1340, 1213,
1146, 1117, 1036, 994, 824, 755, 649, 535 cm-1; HRMS (ESI-TOF) calcd
for C24H23O11 [M+H]+ 487.1240, found 487.1235.
3’,5’,4”-O-Trimethyl-epigallocatechin-3-gallate(10)
Yield 57%; TLC Rf 0.52 (CHCl3/methanol = 3/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) d 6.92 (s, 2H), 6.75
(s, 2H), 5.97 (d, J = 2.4 Hz, 1H), 5.95 (d, J = 2.4 Hz, 1H), 5.44 (br s, 1H),
5.06 (s, 1H), 3.70 (s, 3H), 3.63 (s, 6H), 2.97 (dd, Jgem = 17.9 Hz, J = 4.3 Hz,
1H), 2.81 (ddd, Jgem = 17.9 Hz, J = 1.4 Hz, 1H); FT-IR (solid) 3337, 1697,
1606, 1517, 1461, 1433, 1372, 1223, 1147, 1113, 1057, 824, 755, 665, 531 cm-1;
HRMS (ESI-TOF) calcd for C25H25O11 [M+H]+
501.1397, found 501.1400.
3’,5’,3”,4”-O-Tetramethyl-epigallocatechin-3-gallate (11)
Yield 60%; TLC Rf 0.43 (CHCl3/methanol = 4/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.06 (d, J = 1.4 Hz, 1H), 6.94 (d, J = 1.4 Hz, 1H), 6.78 (s, 2H), 6.00 (d, J =
1.9 Hz, 1H), 5.97 (d, J = 1.9 Hz, 1H), 5.50 (br s, 1H), 5.10 (s, 1H), 3.71 (s,
3H), 3.70 (s, 3H), 3.64 (s, 6H), 2.99 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H),
2.86 (d, Jgem = 17.9 Hz, 1H); HRMS (ESI-TOF) calcd for C26H27O11
[M+H]+ 515.1553, found 515.1552.
3’,5’,3”,5”-O-Tetramethyl-epigallocatechin-3-gallate (12)
Yield 61%; TLC Rf 0.43 (CHCl3/methanol = 4/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.10 (s, 2H), 6.79 (s, 2H), 6.00 (d, J = 1.9 Hz, 1H), 5.98 (d, J = 2.4 Hz, 1H),
5.51 (br s, 1H, e), 5.12 (s, 1H), 3.72 (s, 6H), 3.63 (s, 6H), 3.00 (dd, Jgem =
17.9 Hz, J = 4.8 Hz, 1H), 2.87 (dd, Jgem = 17.9 Hz, J = 1.9 Hz, 1H); FT-IR
(solid) 3386, 1693, 1602, 1512, 1461, 1423, 1328, 1211, 1146, 1108, 997, 955,
911, 864, 817, 759, 636 cm-1; HRMS (ESI-TOF) calcd for C26H27O11
[M+H]+ 515.1553, found 515.1552.
3’,4’,5’-O-Trimethyl-epigallocatechin-3-gallate (13)
Yield 58%; TLC Rf 0.38 (CHCl3/methanol =
4/1); 1H NMR (400 MHz, acetone-d6/D2O = 2/1) d
6.93 (s, 2H), 6.80 (s, 2H), 6.05 (s, 1H), 6.04 (s, 1H), 5.43 (br s, 1H), 5.10
(s, 1H), 3.65 (s, 6H), 3.65 (s, 3H), 2.94 (dd, Jgem = 17.4 Hz, J = 4.3 Hz, 1H),
2.79 (d, Jgem = 17.9 Hz, 1H); FT-IR (solid) 3287, 1682, 1598, 1533, 1505, 1459,
1421, 1368, 1329, 1234, 1193, 1146, 1117, 1031, 997, 968, 874, 818, 721, 586 cm-1;
HRMS (ESI-TOF) calcd for C25H25O11 [M+H]+ 501.1397,
found 501.1397.
3’,4’,5’,4”-O-Tetramethyl-epigallocatechin-3-gallate (14)
Yield 52%; TLC Rf 0.42 (CHCl3/methanol = 4/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.95 (s, 2H), 6.83 (s, 2H), 6.02 (d, J = 1.9 Hz, 1H), 5.99 (d, J = 1.9 Hz, 1H),
5.51 (br s, 1H), 5.14 (s, 1H), 3.74 (s, 3H), 3.67 (s, 6H), 3.61 (s, 3H), 3.01
(dd, Jgem = 17.9 Hz, J = 4.3 Hz 1H), 2.87 (d, Jgem = 17.9 Hz, 1H); HRMS
(ESI-TOF) calcd for C26H27O11 [M+H]+ 515.1553,
found 515.1556.
3’,4’,5’,3”,4”-O-Pentamethyl-epigallocatechin-3-gallate (15)
Yield 49%; TLC Rf 0.54 (CHCl3/methanol = 4/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.07 (d, J = 1.9 Hz, 1H), 6.94 (d, J = 1.9 Hz, 1H), 6.83 (s, 2H), 6.02 (d, J =
2.4 Hz, 1H), 5.99 (d, J = 2.4 Hz, 1H), 5.54 (br s, 1H), 5.16 (s, 1H), 3.73 (s,
3H), 3.72 (s, 3H), 3.66 (s, 6H, j), 3.61 (s, 3H), 3.01 (dd, Jgem = 17.4 Hz, J =
3.9 Hz, 1H), 2.89 (dd, Jgem = 16.4 Hz, J = 0.97 Hz, 1H); HRMS (ESI-TOF) calcd
for C27H29O11 [M+H]+ 529.1710, found 529.1716.
3’,4’,5’,3”,5”-O-Pentamethyl-epigallocatechin-3-gallate (16)
Yield 50%; TLC Rf 0.55 (CHCl3/methanol = 4/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.06 (s, 2H), 6.82 (s, 2H), 6.08 (d, J = 2.4 Hz, 1H), 6.05 (d, J = 1.9 Hz, 1H),
5.54 (br s, 1H), 5.16 (s, 1H), 3.70 (s, 6H), 3.66 (s, 3H), 3.64 (s, 6H), 3.04
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.84 (dd, Jgem = 17.4 Hz, J = 1.4 Hz 1H);
HRMS (ESI-TOF) calcd for C27H29O11 [M+H]+
529.1710, found 529.1712.
5-O-Methyl-epigallocatechin-3-gallate (17)
Yield 40%; TLC Rf 0.37 (CHCl3/methanol = 3/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.94 (d, J = 2.9 Hz, 2H), 6.58 (d, J = 2.4 Hz, 2H), 6.03 (s, 1H), 6.01 (s, 1H),
5.33 (br s, 1H), 4.95 (s, 1H), 3.64 (s, 3H), 2.91 (dd, Jgem = 17.9 Hz, J = 1.9
Hz), 2.72 (d, Jgem = 17.4 Hz, 1H); FT-IR (solid) 3271, 2962, 1654, 1601, 1513,
1432, 1370, 1200, 1145, 1118, 1042, 799, 668, 524 cm-1; HRMS
(ESI-TOF) calcd for C23H21O11 [M+H]+ 473.1084,
found 473.1084.
5,4”-O-Dimethyl-epigallocatechin-3-gallate (18)
Yield 37%; TLC Rf 0.46 (CHCl3/methanol =
3/1); 1H NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.91 (s, 2H), 6.58 (s, 2H), 6.03 (s, 1H), 6.02 (s, 1H), 5.29 (br s, 1H), 5.13
(s, 1H), 3.71 (s, 3H), 3.65 (s, 3H), 2.83 (dd, Jgem = 17.4 Hz, J = 4.4 Hz, 1H),
2.72 (d, Jgem = 17.4 Hz, 1H); FT-IR (solid) 3401, 1627, 1444, 1371, 1212, 1043,
866, 621, 481 cm-1; HRMS (ESI-TOF) calcd for C24H23O11
[M+H]+ 487.1240, found 487.1230.
5,3”,4”-O-Trimethyl-epigallocatechin-3-gallate (19)
Yield 56%; TLC Rf 0.55 (CHCl3/methanol = 4/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.04 (d, J = 1.9 Hz, 1H), 6.95 (d, J = 1.9 Hz, 1H), 6.60 (s, 2H), 6.06 (d, J =
1.9 Hz, 1H), 6.03 (d, J = 1.9 Hz, 1H), 5.40 (br s, 1H), 5.02 (s, 1H), 3.76 (s,
3H) 3.71 (s, 3H), 3.66 (s, 3H), 2.83 (dd, Jgem = 17.9 Hz, J = 4.4 Hz, 1H), 2.72
(d, Jgem = 17.9 Hz, 1H); 13C NMR (100 MHz, acetoned6/D2O
= 2/1) δ 166.2, 159.4, 157.5, 156.0, 153.5, 150.6,
145.9, 141.3, 130.1, 125.8, 111.2, 106.1, 105.6, 99.1, 96.1, 92.7, 77.4, 70.2,
60.6, 56.2, 55.6, 25.9; FT-IR (solid) 3332, 1693, 1595, 1534, 1506, 1463, 1426,
1364, 1338, 1195, 1140, 1111, 1029, 1003, 821, 761, 667, 524 cm-1;
HRMS (ESI-TOF) calcd for C25H25O11 [M+H]+
501.1397, found 501.1394.
5,3”,5”-O-Trimethyl-epigallocatechin-3-gallate (20)
Yield 33%; TLC Rf 0.54 (CHCl3/methanol =
4/1); 1H NMR (400 MHz, acetone-d6/D2O = 2/1) δ 7.06 (s,
2H), 6.59 (s, 2H), 6.05 (s, 1H), 6.02 (s, 1H), 5.35 (br s, 1H), 5.02 (s, 1H),
3.74 (s, 6H), 3.65 (s, 3H), 2.94 (d, Jgem = 18.4 Hz, 1H), 2.72 (d, Jgem = 18.4
Hz, 1H); FT-IR (solid) 3232, 1688, 1607, 1532, 1513, 1463, 1425, 1364, 1331,
1212, 1144, 1112, 1029, 958, 913, 821, 760, 738, 551 cm-1; HRMS
(ESI-TOF) calcd for C25H25O11 [M+H]+
501.1397, found 501.1392.
5,4’-O-Dimethyl-epigallocatechin-3-gallate (21)
Yield 68%; TLC Rf 0.47 (CHCl3/methanol = 4/1); 1H NMR (400
MHz, acetone-d6/D2O = 2/1) d 6.95 (s, 2H), 6.60 (s, 2H),
6.05 (d, J = 2.4 Hz, 1H), 6.03 (d, J = 2.4 Hz, 1H), 5.38 (br s, 1H), 4.99 (s,
1H), 3.66 (s, 3H), 3.65 (s, 3H), 2.93 (dd, Jgem = 17.9 Hz, J = 4.4 Hz, 1H),
2.82 (d, Jgem = 17.9 Hz, 1H); 13C NMR (100 MHz, acetone-d6/D2O
= 2/1) δ 166.7, 159.3, 157.0, 155.7, 150.3, 145.4,
135.3, 134.8, 120.6, 109.7, 106.5, 99.2, 96.0, 92.7, 77.4, 69.4, 60.5, 55.6,
25.9; FT-IR (solid) 3299, 1689, 1605, 1529, 1506, 1441, 1315, 1233, 1195, 1143,
1116, 1029, 1007, 820, 766, 628 cm-1; HRMS (ESI-TOF) calcd for C24H23O11
[M+H]+ 487.1240, found 487.1260.
5,4’,4”-O-Trimethyl-epigallocatechin-3-gallate (22)
Yield 55%; TLC Rf 0.57 (CHCl3/methanol = 4/1); 1H NMR (400
MHz, acetone-d6/D2O = 2/1) δ 6.87
(s, 2H), 6.57 (s, 2H), 6.02 (d, J = 2.4 Hz, 1H), 6.00 (d, J = 2.4 Hz, 1H), 5.37
(br s, 1H), 4.97 (s, 1H), 3.68 (s, 3H), 3.62 (s, 3H), 3.62 (s, 3H), 2.93 (dd, Jgem
= 17.4 Hz, J = 4.4 Hz, 1H), 2.82 (d, Jgem = 17.4!Hz, 1H); 13C NMR
(100 MHz, acetone-d6/D2O = 2/1) δ
166.2, 159.3, 157.2, 155.7, 150.7, 150.5, 140.4, 135.3, 134.8, 125.6, 109.5,
106.4, 99.0, 96.0, 92.6, 77.3, 69.7, 60.4, 55.5, 25.9; FT-IR (solid) 3315,
1693, 1601, 1524, 1506, 1436, 1343, 1140, 1113, 1042, 990, 843, 816, 760, 714,
645, 530 cm-1; HRMS (ESI-TOF) calcd for C25H25O11
[M+H]+ 501.1397, found 501.1397.
5,4’,3”,4”-O-Tetramethyl-epigallocatechin-3-gallate (23)
Yield 67%; TLC Rf 0.65 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.98 (d, J = 1.9 Hz, 1H), 6.90 (d, J = 1.9 Hz, 1H), 6.58 (s, 2H), 6.03 (d, J =
2.4 Hz, 1H), 6.01 (d, J = 1.9 Hz, 1H), 5.38 (br s, 1H), 5.01 (s, 1H), 3.72 (s,
3H), 3.68 (s, 3H), 3.63 (s, 3H), 3.63 (s, 3H), 2.93 (dd, Jgem = 17.9 Hz, J =
4.4 Hz, 1H), 2.84 (d, Jgem = 17.9 Hz, 1H); 13C NMR (100 MHz,
acetone-d6/D2O = 2/1) δ 166.2,
159.3, 157.4, 155.7, 153.4, 150.6, 150.5, 141.2, 135.3, 134.9, 125.6, 111.1,
106.2, 105.4, 98.9, 95.9, 92.6, 77.2, 70.1, 60.6, 60.4, 5 6.1, 55.5, 25.7;
FT-IR (solid) 3401, 1686, 1598, 1512, 1459, 1425, 1358, 1326, 1201, 1139, 1110,
1044, 1002, 955, 911, 864, 819, 757, 717, 621 cm-1; HRMS (ESI-TOF)
calcd for C26H27O11 [M+H]+ 515.1553, found
515.1567.
5,4’,3”,5”-O-Tetramethyl-epigallocatechin-3-gallate (24)
Yield 61%; TLC Rf 0.64 (CHCl3/methanol = 5/1); 1H NMR (400
MHz, acetone-d6) δ 7.10 (s, 2H), 6.63 (s,
2H), 6.08 (d, J = 2.4 Hz, 1H), 6.05 (d, J = 2.4 Hz, 1H), 5.40 (br s, 1H), 5.08
(s, 1H), 3.84 (s, 6H), 3.77 (s, 3H), 3.68 (s, 3H), 2.98 (dd, Jgem = 17.9 Hz, J =
4.4 Hz, 1H), 2.84 (dd, Jgem = 17.9 Hz, J = 2.9 Hz 1H); 13C NMR (100
MHz, acetone-d6/D2O = 2/1) δ
166.6, 159.3, 157.4, 155.7, 150.6, 147.9,135.3, 135.0,!120.4, 107.3, 106.5,
106.1, 99.0, 95.9, 92.6, 77.1, 70.1, 60.4, 56.3, 55.5, 25.6; FTIR (solid) 3401,
1686, 1598, 1512, 1459, 1425, 1358, 1326, 1201, 1139, 1110, 1044, 1002, 955,
911, 864, 819, 757, 717, 621 cm-1; HRMS (ESI-TOF) calcd for C26H27O11
[M+H]+ 515.1553, found 515.1555.
5,3’,5’-O-Trimethyl-epigallocatechin-3-gallate (25)
Yield 54%; TLC Rf 0.29 (CHCl3/methanol
= 5/1); 1H NMR (400 MHz, acetone-d6/D2O = 2/1)
δ 6.96 (s, 2H), 6.77 (s, 2H), 6.05 (s, 1H), 6.04 (s, 1H), 5.43 (br s, 1H), 5.06
(s, 1H), 3.65 (s, 3H), 3.64 (s, 6H), 2.94 (dd, Jgem = 17.4 Hz, J = 4.3 Hz, 1H),
2.79 (d, Jgem = 17.4 Hz, 1H); FT-IR (solid) 3335, 1687, 1606, 1519, 1460, 1314,
1211, 1143, 1111, 1030, 996, 967, 911, 874, 819, 767, 663, 634, 544 cm-1;
HRMS (ESI-TOF) calcd for C25H28NO11 [M+NH4]+
518.1662, found 518.1675.
5,3’,5’,4”-O-Tetramethyl-epigallocatechin-3-gallate (26)
Yield 60%; TLC Rf 0.34 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.91 (d, J = 2.4 Hz, 2H), 6.75 (d, J = 2.4 Hz, 2H), 6.05 (s, 1H), 6.05 (s, 1H),
5.45 (br s, 1H), 5.08 (s, 1H), 3.70 (s, 3H), 3.65 (s, 3H), 3.63 (s, 6H), 2.96
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.80 (d, Jgem = 17.9 Hz, 1H); 13C
NMR (100 MHz, acetone-d6/D2O = 2/1) δ 165.7,
159.6, 157.7, 156.2, 151.0, 148.1,140.4, 129.5, 125.7, 118.2, 109.5, 104.7,
99.1, 96.1, 92.7, 78.0, 69.6, 60.4, 56.2, 55.6, 26.2; FTIR (solid) 3371, 1696,
1600, 1519, 1458, 1429, 1346, 1233, 1200, 1144, 1110, 1053, 996, 966, 912, 820,
744, 714, 624 cm-1; HRMS (ESI-TOF) calcd for C26H27O11
[M+H]+ 515.1553, found 515.1546.
5,3’,5’,3”,4”-O-Pentamethyl-epigallocatechin-3-gallate (27)
Yield 58%; TLC Rf 0.54 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.05 (d, J = 1.9 Hz, 1H), 6.92 (d, J = 1.9 Hz, 1H), 6.77 (s, 2H), 6.06 (s, 1H),
6.05 (s, 1H), 5.49 (br s, 1H), 5.10 (s, 1H), 3.71 (s, 3H), 3.70 (s, 3H), 3.70
(s, 3H), 3.63 (s, 6H), 2.97 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.83 (dd, Jgem
= 17.9 Hz, J = 1.4 Hz, 1H); 13C NMR (100 MHz, acetone-d6/D2O
= 2/1) δ 165.7, 159.5, 157.7, 156.1, 153.7, 150.8,
148.1, 141.5, 135.7, 129.5, 125.7, 111.3, 105.5, 104.7, 99.0, 96.1, 92.7, 77.9,
69.9, 60.7, 56.2, 56.2, 55.6, 26.2; FT-IR (solid) 3379, 1697, 1603, 1503, 1459,
1427, 1341, 1213, 1144, 1107, 1029, 996, 957, 910, 871, 821, 761, 746, 720,
665, 632, 533 cm-1; HRMS (ESI-TOF) calcd for C27H29O11
[M+H]+ 529.1710, found 529.1727.
5,3’,5’,3”,5”-O-Pentamethyl-epigallocatechin-3-gallate (28)
Yield 49%; TLC Rf 0.54 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6) δ 7.18 (s, 2H),
6.86 (s, 2H), 6.14 (d, J = 1.9 Hz, 1H), 6.10 (d, J = 1.9 Hz, 1H), 5.59 (br s,
1H), 5.20 (s, 1H), 3.79 (s, 6H), 3.74 (s, 3H), 3.69 (s, 6H), 3.04 (dd, Jgem =
17.9 Hz, J = 4.8 Hz, 1H), 2.84 (dd, Jgem = 17.9 Hz, J = 1.9 Hz, 1H); FT-IR
(solid) 3386, 1693, 1602, 1512, 1461, 1423, 1328, 1211, 1146, 1108, 997, 955,
911, 864, 817, 759, 636 cm-1; HRMS (ESI-TOF) calcd for C27H29O11
[M+H]+ 529.1710, found 529.1689.
5,3’,4’,5’-O-Tetramethyl-epigallocatechin-3-gallate (29)
Yield 55%; TLC Rf 0.32 (CHCl3/methanol
= 7/1); 1H NMR (400 MHz, acetone-d6/D2O = 2/1)
δ 6.93 (s, 2H), 6.80 (s, 2H), 6.05 (s, 1H), 6.04 (s, 1H), 5.43 (br s, 1H), 5.10
(s, 1H), 3.65 (s, 6H), 3.65 (s, 3H),3.59 (s, 3H), 2.94 (dd, Jgem = 17.4 Hz, J =
4.3 Hz, 1H), 2.79 (d, Jgem = 17.9 Hz, 1H); FT-IR (solid) 3287, 1682, 1598,
1533, 1505, 1459, 1421, 1368, 1329, 1234, 1193, 1146, 1117, 1031, 997, 968,
874, 818, 721, 586 cm-1; HRMS (ESI-TOF) calcd for C26H30NO11
[M+NH4]+ 532.1819, found 532.1842.
5,3’,4’,5’,4”-O-Pentamethyl-epigallocatechin-3-gallate (30)
Yield 53%; TLC Rf 0.37 (CHCl3/methanol = 7/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.88 (d, J = 3.4 Hz, 2H), 6.78 (d, J = 2.9 Hz, 2H), 6.04 (s, 1H), 6.04 (s,
1H5.46 (br s, 1H), 5.10 (s, 1H), 3.68 (s, 3H), 3.64 (s, 6H), 3.59 (s, 3H), 3.58
(s, 3H), 2.95 (d, Jgem = 17.9 Hz, 1H), 2.80 (d, Jgem = 17.9 Hz, 1H); 13C
NMR (100 MHz, acetone-d6/D2O = 2/1) δ
165.7, 159.4,157.5, 155.9, 153.3, 150.9, 140.5, 137.7, 125.5, 109.5, 104.5,
99.0, 96.1, 92.7, 78.8, 77.8,!69.5, 60.5, 60.4,!56.0, 55.6, 26.1; FT-IR (solid)
3375, 1698, 1593, 1502, 1459, 1343, 1230, 1116, 1058, 995, 968, 922, 872, 815,
759, 731, 714, 670, 631 cm-1; HRMS (ESI-TOF) calcd for C28H31O11
[M+H]+ 529.1710, found 529.1732.
5,3’,4’,5’,3”,4”-O-Hexamethyl-epigallocatechin-3-gallate
(31)
Yield 73%; TLC Rf 0.53 (CHCl3/methanol =
9/1); 1H NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.03 (d, J = 1.9 Hz, 1H), 6.91 (d, J = 1.9 Hz, 1H), 6.80 (s, 2H), 6.07 (d, J =
2.4 Hz, 1H), 6.05 (d, J = 1.9 Hz, 1H), 5.51 (br s, 1H), 5.14 (s, 1H), 3.70 (s,
3H), 3.69 (s, 3H), 3.66 (s, 3H), 3.64 (s, 6H), 3.59 (s, 3H), 2.98 (dd, Jgem =
17.9 Hz, J = 4.3 Hz, 1H), 2.83 (d, Jgem = 17.4 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 165.2, 159.0, 155.6, 155.3, 153.0, 151.9, 148.7,
139.5, 137.6, 133.4, 125.4, 109.8, 105.9, 103.7, 99.8, 96.0, 92.1, 77.8, 68.7,
61.0, 60.8, 56.0, 55.9, 55.4, 25.9; FT-IR (solid) 3368, 1709, 1591, 1503, 1458,
1421, 1366, 1343, 1196, 1145, 1119, 1035, 999, 945, 813, 757, 720, 671, 629 cm-1;
HRMS (ESI-TOF) calcd for C28H31O11 [M+H]+
543.1866, found 543.1887.
5,3’,4’,5’,3”,5”-O-Hexamethyl-epigallocatechin-3-gallate
(32)
Yield 69%; TLC Rf 0.53 (CHCl3/methanol =
9/1); 1H NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.06 (s, 2H), 6.82 (s, 2H), 6.08 (d, J = 2.4 Hz, 1H), 6.05 (d, J = 1.9 Hz, 1H),
5.54 (br s, 1H), 5.16 (s, 1H), 3.70 (s, 6H), 3.66 (s, 3H), 3.64 (s, 6H), 3.60
(s, 3H), 3.04 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.84 (dd, Jgem = 17.4 Hz, J
= 1.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 165.4, 158.8,
156.6, 155.3, 152.9, 146.8, 139.9, 133.5, 120.5, 106.9, 103.9, 99.1,
95.5,,92.2, 77.6, 68.5, 60.7, 56.2, 55.8, 55.2, 50.2, 25.8; FT-IR (solid) 3378,
1708, 1597, 1504, 1461, 1421, 1358, 1327, 1279, 1211, 1118, 1034, 1002, 955,
955, 914, 866, 819, 759, 721, 668, 632, 528 cm-1; HRMS (ESI-TOF)
calcd for C28H31O11 [M+H]+
543.1866, found 543.1865.
7-O-Methyl-epigallocatechin-3-gallate (33)
Yield 36%; TLC Rf 0.19 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.92 (s, 2H), 6.58 (s, 2H), 6.15 (s, 1H), 6.12 (s, 1H), 5.36 (br s, 1H), 4.99
(s, 1H), 3.67 (s, 3H), 2.91 (dd, Jgem = 17.9 Hz, J = 1.9 Hz, 1H), 2.72 (d, Jgem
= 17.4 Hz, 1H); FT-IR (solid) 3264, 1686, 1616, 1594, 1533, 1499, 1440, 1368,
1340, 1192, 1144, 1114, 1030, 884, 816, 737, 698, 630, 477 cm-1;
HRMS (ESI-TOF) calcd for C23H21O11 [M+H]+
473.1084, found 473.1070.
7,4”-O-Dimethyl-epigallocatechin-3-gallate (34)
Yield 43%; TLC Rf 0.31 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.89 (s, 2H), 6.58 (s, 2H), 6.02 (d, J = 1.9 Hz, 1H), 5.99 (d, J = 2.4 Hz, 1H),
5.38 (br s, 1H), 4.98 (s, 1H), 3.69 (s, 3H), 3.62 (s, 3H), 2.95 (dd, Jgem =
17.9 Hz, J = 4.3 Hz, 1H), 2.84 (d, Jgem = 17.9 Hz, 1H); FT-IR (solid) 3304,
1694, 1619, 1596, 1516, 1438, 1373, 1342, 1231, 1192, 1142, 1039, 871, 759,
710, 668, 541 cm-1; HRMS (ESI-TOF) calcd for C24H23O11
[M+H]+ 487.1240, found 487.1223.
7,3”,4”-O-Trimethyl-epigallocatechin-3-gallate (35)
Yield 45%; TLC Rf 0.45 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) d 7.06 (s, 1H), 7.06
(d, J = 1.9 Hz, 0.5H), 6.95 (d, J = 1.9 Hz, 0.5H), 6.60 (s, 2H), 6.06 (d, J =
1.9 Hz, 1H), 6.03 (d, J = 1.9 Hz, 1H), 5.40 (br s, 1H), 5.02 (s, 1H), 3.76 (s,
3H), 3.71 (s, 3H), 3.66 (s, 3H), 2.83 (dd, Jgem = 17.9 Hz, J = 4.4 Hz, 1H),
2.72 (d, Jgem = 17.9 Hz, 1H); FT-IR (solid) 3357, 1686, 1619, 1595, 1514, 1448,
1426, 1362, 1330, 1196, 1145, 1112, 1039, 868, 821, 765, 639, 626, 554, 503 cm-1;
HRMS (ESI-TOF) calcd for C25H25O11 [M+H]+
501.1397, found 501.1394.
7,3”,5”-O-Trimethyl-epigallocatechin-3-gallate (36)
Yield 40%; TLC Rf 0.44 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.04 (s, 2H), 6.59 (s, 2H), 6.03 (d, J = 2.4 Hz, 1H), 6.02 (d, J = 2.4 Hz, 1H),
5.36 (br s, 1H), 5.03 (s, 1H), 3.72 (s, 6H), 3.61 (s, 3H), 2.94 (d, Jgem = 17.9
Hz, 1H), 2.72 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C NMR (100 MHz, acetone-d6/D2O
= 2/1) δ 166.7, 159.7, 156.9, 156.2, 147.8, 145.8,
132.6, 130.2, 120.4, 120.3, 107.3, 105.9, 99.5, 94.9, 93.4, 77.4, 70.3, 56.3,
55.3, 25.7; FT-IR (solid) 3366, 1686, 1618, 1597, 1514, 1460, 1425, 1325, 1183,
1144, 1112, 1035, 996, 962, 912, 818, 756, 734, 538 cm-1; HRMS
(ESITOF) calcd for C25H25O11 [M+H]+ 501.1397,
found 501.1399.
7,4’-O-Dimethyl-epigallocatechin-3-gallate (37)
Yield 48%; TLC Rf 0.29 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) d 6.97 (s, 2H), 6.63
(s, 2H), 6.07 (d, J = 2.4 Hz, 1H), 6.02 (d, J = 2.4 Hz, 1H), 5.42 (br s, 1H),
5.03 (s, 1H), 3.68 (s, 3H), 3.65 (s, 3H), 2.99 (dd, Jgem = 17.9 Hz, J = 4.4 Hz,
1H), 2.89 (d, Jgem = 17.9 Hz, 1H); 13C NMR (100 MHz, acetone-d6/D2O
= 2/1) δ 166.7, 159.7, 156.9, 156.2, 150.4, 145.5,
138.9, 135.3,134.8, 120.6, 109.7, 106.5, 99.6, 95.0, 93.5, 77.5, 69.5, 60.5,
55.3, 26.0; FT-IR (solid) 3340, 1686, 1596, 1512, 1444, 1317, 1193, 1144, 1034,
973, 819, 768, 684, 648 cm-1; HRMS (ESI-TOF) calcd for C24H23O11
[M+H]+ 487.1240, found 487.1250.
7,4’,4”-O-Trimethyl-epigallocatechin-3-gallate (38)
Yield 47%; TLC Rf 0.55 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.90 (s, 2H), 6.61 (s, 2H), 6.05 (d, J = 2.4 Hz, 1H), 6.01 (d, J = 2.4 Hz, 1H),
5.43 (br s, 1H), 5.02 (s, 1H), 3.71 (s, 3H), 3.66 (s, 3H), 3.64 (s, 3H), 2.98
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.87 (d, Jgem = 17.9 Hz, 1H); FT-IR
(solid) 3333, 1692, 1624, 1592, 1513, 1434, 1376, 1233, 1194, 1145, 1044, 987,
818, 757, 711, 525 cm-1; HRMS (ESI-TOF) calcd for C25H25O11
[M+H]+ 501.1397, found 501.1405.
7,4’,3”,4”-O-Tetramethyl-epigallocatechin-3-gallate (39)
Yield 50%; TLC Rf 0.36 (CHCl3/methanol = 9/1); 1H
NMR (270 MHz, acetone-d6/D2O = 2/1) δ
7.01 (d, J = 1.9 Hz, 1H), 6.92 (d, J = 1.9 Hz, 1H), 6.61 (s, 2H), 6.05 (d, J =
2.0 Hz, 1H), 6.01 (d, J = 2.0 Hz, 1H), 5.42 (br s, 1H), 5.05 (s, 1H), 3.74 (s,
3H), 3.69 (s, 3H), 3.65 (s, 3H), 3.63 (s, 3H), 2.93 (dd, Jgem = 17.1 Hz, J =
4.0 Hz, 1H), 2.84 (d, Jgem = 17.1 Hz, 1H); FT-IR (solid) 3357, 1696, 1623,
1591, 1509, 1430, 1365, 1343, 1192, 1143, 1101, 1045, 998, 945, 815, 757, 712,
538 cm-1; HRMS (ESI-TOF) calcd for C26H27O11
[M+H]+ 515.1553, found 515.1578.
7,4’,3”,5”-O-Tetramethyl-epigallocatechin-3-gallate (40)
Yield 39%; TLC Rf 0.35 (CHCl3/methanol = 9/1); 1H
NMR (270 MHz, acetone-d6/D2O = 2/1) δ
7.03 (s, 2H), 6.60 (s, 2H), 6.03 (d, J = 1.9 Hz, 1H), 6.01 (d, J = 1.9 Hz, 1H),
5.37 (br s, 1H), 5.06 (s, 1H), 3.72 (s, 6H), 3.62 (s, 3H), 3.61 (s, 3H), 2.96
(br s, 1H) , 2.95 (br s, 1H); 13C NMR (67.8 MHz, acetone-d6/D2O
= 2/1) δ 166.6, 159.8, 157.0, 156.1, 150.6, 147.9,
135.3, 135.0, 120.5, 107.3, 106.1, 99.5, 94.9, 93.4, 77.3, 70.2, 60.4, 56.4,
55.3, 25.7; FT-IR (solid) 3408, 1685, 1595, 1512, 1426, 1363, 1330, 1184, 1144,
1115, 997, 817, 752, 713, 554 cm-1; HRMS (ESI-TOF) calcd for C26H27O11
[M+H]+ 515.1553, found 515.1567
7,3’,5’-O-Trimethyl-epigallocatechin-3-gallate (41)
Yield 55%; TLC Rf 0.50 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.90 (s, 2H), 6.75 (s, 2H), 6.05 (d, J = 2.4 Hz, 1H), 6.01 (d, J = 1.9 Hz, 1H),
5.46 (br s, 1H), 5.09 (s, 1H), 3.69 (s, 3H), 3.63 (s, 6H), 2.99 (dd, Jgem =
17.4 Hz, J = 3.9 Hz, 1H), 2.83 (d, Jgem = 16.9 Hz, 1H); FT-IR (solid) 3373,
1681, 1619, 1595, 1517, 1430, 1348, 1195, 1144, 1111, 1056, 994, 914, 872, 822,
761, 713, 524 cm-1; HRMS (ESI-TOF) calcd for C25H25O11
[M+H]+ 501.1397, found 501.1388.
7,3’,5’,4”-O-Tetramethyl-epigallocatechin-3-gallate (42)
Yield 65%; TLC Rf 0.56 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.89 (s, 2H), 6.75 (s, 2H), 6.04 (d, J = 2.4 Hz, 1H), 6.02 (d, J = 2.4 Hz, 1H),
5.45 (br s, 1H), 5.08 (s, 1H, f), 3.68 (s, 3H), 3.64 (s, 3H), 3.62 (s, 6H),
2.99 (dd, Jgem = 17.9 Hz, J = 4.4 Hz, 1H), 2.82 (d, Jgem = 16.9 Hz, 1H); 13C
NMR (67.8 MHz, acetone-d6/D2O = 2/1) δ
165.8, 159.8, 157.0, 156.4, 150.9, 148.0, 140.5, 135.4, 129.4, 125.6, 109.6,
104.6, 99.6, 95.0, 93.5, 78.0, 69.7, 60.4, 56.2, 55.3, 26.2; FTIR (solid) 3343,
1685, 1619, 1592, 1514, 1448, 1434, 1344, 1212, 1144, 1113, 1056, 995, 973,
911, 872, 821,759, 739, 712, 585 cm-1; HRMS (ESI-TOF) calcd for C26H27O11
[M+H]+ 515.1553, found 515.1556.
7,3’,5’,3’,4”-O-Pentamethyl-epigallocatechin-3-gallate (43)
Yield 59%; TLC Rf 0.50 (CHCl3/methanol = 9/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.08 (d, J = 1.9 Hz, 1H), 6.95 (d, J = 1.9 Hz, 1H), 6.81 (s, 2H), 6.09 (d, J =
1.9 Hz, 1H), 6.05 (d, J = 1.9 Hz, 1H), 5.54 (br s, 1H), 5.15 (s, 1H), 3.73 (s,
3H), 3.72 (s, 3H), 3.66 (s, 3H), 3.66 (s, 6H), 3.04 (dd, Jgem = 17.9 Hz, J =
4.3 Hz, 1H), 2.90 (dd, Jgem = 17.9 Hz, J = 0.97 Hz, 1H); 13C NMR
(67.8 MHz, CDCl3) δ 165.2, 159.4, 155.9,
155.0, 151.9, 148.7, 146.8, 139.5, 134.5, 128.8, 125.3, 109.8, 106.0, 103.5,
98.9, 95.5, 94.2, 77.9, 68.8, 61.0, 56.1, 56.0, 55.3, 25.7; FT-IR (solid) 3372,
1698, 1619, 1592, 1510, 1454, 1426, 1341, 1216, 1199, 1145, 1108, 1033, 995,
981, 913, 872, 821, 759, 728, 712, 526 cm-1; HRMS (ESI-TOF) calcd
for C27H29O11 [M+H]+ 529.1710, found 529.1704.
7,3’,5’,3’,5”-O-Pentamethyl-epigallocatechin-3-gallate (44)
Yield 62%; TLC Rf 0.49 (CHCl3/methanol = 9/1); 1H
NMR (400 MHz, CDCl3) δ 7.19 (s, 2H), 6.69
(s, 2H), 6.24 (d, J = 2.4 Hz, 1H), 6.06 (d, J = 2.4 Hz, 1H), 5.67 (br s, 1H),
5.09 (s, 1H), 3.85 (s, 6H), 3.76 (s, 3H), 3.73 (s, 6H), 3.04 (dd, Jgem = 16.9
Hz, J = 4.3 Hz, 1H), 2.84 (dd, Jgem = 17.4 Hz, J = 2.4 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 165.3, 159.5, 156.1,
155.0, 151.9, 146.9, 146.6, 139.6, 134.7, 128.8, 120.9, 107.0, 103.7, 99.1,
95.3, 94.2, 77.9, 68.4, 56.4, 56.2, 55.4, 25.7; FT-IR (solid) 3371, 1698, 1594,
1513, 1459, 1423, 1353, 1329, 1205, 1184, 1145, 1111, 1033, 962, 910, 868, 817,
756, 739, 587 cm-1; HRMS (ESI-TOF) calcd for C27H29O11
[M+H]+ 529.1710, found 529.1708.
7,3’,4’,5’-O-Tetramethyl-epigallocatechin-3-gallate (45)
Yield 50%; TLC Rf 0.38 (CHCl3/methanol = 7/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.96 (s, 2H), 6.83 (s, 2H), 6.08 (d, J = 2.4 Hz, 1H), 6.03 (d, J = 2.4 Hz, 1H),
5.48 (br s, 1H), 5.14 (s, 1H), 3.67 (s, 6H), 3.60 (s, 3H), 3.22 (s, 3H), 3.01
(dd, Jgem = 17.4 Hz, J = 4.3 Hz, 1H), 2.86 (d, Jgem = 16.4 Hz, 1H); 13C
NMR (67.8 MHz, acetone-d6/D2O = 2/1) δ
166.2, 159.8, 157.1, 156.3, 153.4, 145.7, 138.9, 137.8, 134.8, 120.6, 109.6,
104.7, 99.7, 95.1, 93.6, 78.1, 69.2, 60.5, 56.1, 55.3, 26.3; FTIR (solid) 3339,
1685, 1593, 1508, 1444, 1422, 1354, 1325, 1227, 1193, 1145, 1125, 1033, 995,
972, 874, 817, 729, 549 cm-1; HRMS (ESI-TOF) calcd for C26H27O11
[M+H]+ 515.1553, found 515.1553.
7,3’,4’,5’,4”-O-Pentamethyl-epigallocatechin-3-gallate (46)
Yield 73%; TLC Rf 0.51 (CHCl3/methanol = 7/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.94 (s, 2H), 6.84 (s, 2H), 6.09 (d, J = 2.4 Hz, 1H), 6.04 (d, J = 2.4 Hz, 1H),
5.52 (br s, 1H), 5.16 (s, 1H), 3.73 (s, 3H), 3.67 (s, 6H), 3.65 (s, 3H), 3.61
(s, 3H), 3.03 (dd, Jgem = 17.4 Hz, J = 4.3 Hz, 1H), 2.89 (d, Jgem = 17.4 Hz,
1H); 13C NMR (100 MHz, acetone-d6/D2O = 2/1) δ 165.5, 159.2, 155.9, 155.7, 153.0, 149.2, 139.0, 137.5,
133.4, 125.1, 109.3, 103.9, 99.1, 95.2, 93.3, 77.9, 68.6, 60.7, 60.6, 55.9,
55.2, 25.8; FT-IR (solid) 3353, 1694, 1628, 1592, 1505, 1446, 1421, 1344, 1227,
1195, 1146, 1123, 1059, 1042, 994, 972, 911, 873, 816, 758, 731, 713, 668, 634
cm-1; HRMS (ESI-TOF) calcd for C27H29O11
[M+H]+ 529.1710, found 529.1707.
7,3’,4’,5’,3”,4”-O-Hexamethyl-epigallocatechin-3-gallate
(47)
Yield 64%; TLC Rf 0.53 (CHCl3/methanol =
9/1); 1H NMR (67.8 MHz, acetone-d6/D2O = 2/1)
δ 7.05 (d, J = 2.0 Hz, 1H), 6.92 (d, J = 2.0 Hz, 1H), 6.84 (s, 2H), 6.09 (d, J =
2.3 Hz, 1H), 6.04 (d, J = 2.3 Hz, 1H), 5.55 (br s, 1H), 5.18 (s, 1H), 3.72 (s,
3H), 3.70 (s, 3H), 3.66 (s, 6H), 3.64 (s, 3H), 3.61 (s, 3H), 3.04 (dd, Jgem =
17.4 Hz, J = 4.3 Hz, 1H), 2.90 (d, Jgem = 17.4 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 165.2, 159.4, 155.8, 155.1, 153.1, 151.9, 148.7,
139.6, 137.6, 133.3, 127.2, 125.3, 109.8, 105.9, 103.8, 98.9, 95.5, 94.2, 77.9,
68.7, 61.0, 60.8, 56.0, 55.3, 25.7; FT-IR (solid) 3385, 1711, 1625, 1590, 1504,
1458, 1420, 1342, 1218, 1198, 1145, 1121, 1098, 1035, 998, 872, 814, 759, 729, 668,
640 cm-1; HRMS (ESI-TOF) calcd for C28H31O11
[M+H]+ 543.1866, found 543.1866.
7,3’,4’,5’,3”,5”-O-Hexamethyl-epigallocatechin-3-gallate
(48)
Yield 68%; TLC Rf 0.52 (CHCl3/methanol =
9/1); 1H NMR (67.8 MHz, acetone-d6/D2O = 2/1)
δ 7.10 (s, 2H), 6.87 (s, 2H), 6.10 (s, 1H), 6.07 (s, 1H), 5.58 (br s, 1H), 5.21
(s, 1H), 3.73 (s, 6H), 3.66 (s, 3H), 3.66 (s, 6H), 3.62 (s, 3H), 3.05 (dd, Jgem
= 17.8 Hz, J = 3.6 Hz, 1H), 2.93 (d, Jgem = 17.8 Hz, 1H); 13C NMR
(67.8 MHz, CDCl3) δ 165.4, 159.5, 156.0, 155.1, 153.1, 146.6, 139.6,
137.9, 133.3, 120.9, 107.0, 104.0, 99.1, 95.4, 94.1, 77.8, 68.4, 60.8, 56.4,
56.0, 55.3, 25.7; FT-IR (solid) 3360, 1708, 1626, 1592, 1510, 1460, 1421, 1355,
1329, 1207, 1185, 1146, 1115, 1035, 1002, 962, 914, 818, 761, 730, 712, 666 cm-1;
HRMS (ESI-TOF) calcd for C28H31O11 [M+H]+
543.1866, found 543.1867.
5,7-O-Dimethyl-epigallocatechin-3-gallate (49)
Yield 42%; TLC Rf 0.46 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.04 (s, 2H), 6.84 (s, 2H), 6.07 (d, J = 1.9 Hz, 1H), 6.04 (d, J = 1.9 Hz, 1H),
5.57 (br s, 1H), 5.16 (s, 1H), 3.82 (s, 3H), 3.71 (s, 3H), 3.07 (dd, Jgem =
17.4 Hz, J = 4.8 Hz), 2.98 (dd, Jgem = 17.4 Hz, J = 1.4 Hz, 1H); FT-IR (solid)
3315, 2943, 2851, 1678, 1602, 1514, 1460, 1434, 1347, 1191, 1144, 1113, 1054,
1016, 819, 800, 760, 663, 653, 511 cm-1; HRMS (ESI-TOF) calcd for C24H23O11
[M+H]+ 487.1240, found 487.1247.
5,7,4”-O-Trimethyl-epigallocatechin-3-gallate (50)
Yield 51%; TLC Rf 0.50 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.98 (s, 2H), 6.64 (s, 2H), 6.17 (d, J = 2.0 Hz, 1H), 6.13 (d, J = 2.0 Hz, 1H),
5.55 (br s, 1H), 5.09 (s, 1H), 3.81 (s, 3H), 3.77 (s, 3H), 3.76 (s, 3H), 3.03
(dd, Jgem = 17.8 Hz, J = 4.6 Hz, 1H), 2.87 (d, Jgem = 17.8 Hz, 1H); FT-IR
(solid) 3260, 2923, 2851, 1693, 1619, 1594, 1525, 1498, 1453, 1437, 1375, 1341,
1215, 1190, 1145, 1120, 1039, 997, 976, 809, 761, 713, 668, 516 cm-1;
HRMS (ESI-TOF) calcd for C25H25O11 [M+H]+
501.1397, found 501.1406.
5,7,3”,4”-O-Tetramethyl-epigallocatechin-3-gallate (51)
Yield 56%; TLC Rf 0.56 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.07 (d, J = 1.9 Hz, 1H), 7.01 (d, J = 1.9 Hz, 1H), 6.66 (s, 2H), 6.18 (d, J =
2.4 Hz, 1H), 6.13 (d, J = 2.4 Hz, 1H), 5.53 (br s, 1H), 5.13 (s, 1H), 3.82 (s,
3H), 3.77 (s, 3H), 3.77 (s, 3H), 3.76 (s, 3H), 3.04 (dd, Jgem = 17.9 Hz, J =
2.4 Hz, 1H), 2.93 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); FT-IR (solid) 3279,
2924, 2851, 1707, 1617, 1594, 1512, 1456, 1427, 1364, 1344, 1198, 1146, 1113,
1034, 997, 810, 760, 653, 516 cm-1; HRMS (ESI-TOF) calcd for C26H30NO11
[M+H]+ 532.1819, found 532.1816.
5,7,3”,5”-O-Tetramethyl-epigallocatechin-3-gallate (52)
Yield 50%; TLC Rf 0.56 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
7.04 (s, 2H), 6.59 (s, 2H), 6.03 (d, J = 2.4 Hz, 1H), 6.02 (d, J = 2.4 Hz, 1H),
5.36 (br s, 1H), 5.03 (s, 1H), 3.72 (s, 6H), 3.61 (s, 3H), 3.61 (s, 3H), 2.94
(d, Jgem = 17.9 Hz, 1H), 2.72 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); FT-IR
(solid) 3354, 2923, 2850, 1685, 1593, 1512, 1455, 1425, 1363, 1330, 1183, 1144,
1110, 1030, 999, 816, 799, 761, 667, 652, 514, 501 cm-1; HRMS
(ESI-TOF) calcd for C26H27O11 [M+H]+ 515.1553,
found 515.1552.
5,7,4’-O-Trimethyl-epigallocatechin-3-gallate (53)
Yield 55%; TLC Rf 0.51 (CHCl3/methanol = 5/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.96 (s, 2H), 6.63 (s, 2H), 6.13 (d, J = 2.4 Hz, 1H), 6.08 (d, J = 2.4 Hz, 1H),
5.41 (br s, 1H), 5.03 (s, 1H), 3.70 (s, 3H), 3.68 (s, 3H), 3.25 (s, 3H), 2.96
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.86 (d, Jgem = 17.9 Hz, 1H); 13C
NMR (100 MHz, acetone-d6/D2O = 2/1) δ
166.6, 160.2, 159.4, 156.0, 150.6, 145.6, 138.9, 135.4, 134.8, 120.8, 109.7,
106.6, 100.5, 94.1, 92.0, 77.7, 69.3, 60.4, 55.7, 55.5, 26.1; FT-IR (solid)
3294, 2942, 2840, 1687, 1595, 1530, 1499, 1452, 1438, 1372, 1335, 1312, 1191,
1142,1119, 1034, 976, 874, 853, 817, 767, 715, 630, 491 cm-1; HRMS
(ESI-TOF) calcd for C25H25O11 [M+H]+ 501.1397,
found 501.1397.
5,7,4’,4”-O-Tetramethyl-epigallocatechin-3-gallate (54)
Yield 39%; TLC Rf 0.43 (CHCl3/methanol = 7/1); 1H
NMR (400 MHz, acetone-d6) δ 6.98 (s, 2H),
6.65 (s, 2H), 6.18 (d, J = 2.4 Hz, 1H), 6.14 (d, J = 2.4 Hz, 1H,), 5.59 (br s,
1H), 5.12 (s, 1H), 3.81 (s, 3H), 3.77 (s, 3H), 3.76 (s, 3H), 3.74 (s, 3H), 3.03
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.90 (dd, Jgem = 17.9 Hz, J = 1.4 Hz,
1H); FT-IR (solid) 3349, 2935, 2844, 1693, 1619, 1594, 1499, 1453, 1435, 1348,
1267, 1216, 1192, 1141, 1117, 1050, 988, 977, 815, 757, 711, 616 cm-1;
HRMS (ESI-TOF) calcd for C26H27O11 [M+H]+
515.1553, found 515.1575.
5,7,4’,3”,4”-O-Pentamethyl-epigallocatechin-3-gallate (55)
Yield 52%; TLC Rf 0.55 (CHCl3/methanol =
7/1); 1H NMR (400 MHz, CDCl3) δ 7.19 (d, J = 1.9 Hz, 1H),
7.08 (d, J = 1.9 Hz, 1H), 6.69 (s, 2H), 6.21 (d, J = 1.9 Hz, 1H), 6.09 (d, J =
1.9 Hz, 1H), 5.53 (br s, 1H), 5.03 (s, 1H), 3.92 (s, 3H), 3.86 (s, 3H), 3.84
(s, 3H), 3.79 (s, 3H), 3.76 (s, 3H), 3.03 (br s, 2H); FT-IR (solid) 3344, 2929,
2849, 1697, 1619, 1592, 1500, 1453, 1427, 1365, 1343, 1217, 1197, 1143, 1108,
1049, 997, 948, 814, 760, 714, 519 cm-1; HRMS (ESI-TOF) calcd for C27H29O11
[M+H]+ 529.1710, found 529.1721.
5,7,4’,3”,5”-O-Pentamethyl-epigallocatechin-3-gallate (56)
Yield 46%; TLC Rf 0.55 (CHCl3/methanol = 7/1); 1H
NMR (400 MHz, CDCl3) δ 7.20 (s, 2H), 6.70
(s, 2H), 6.22 (d, J = 2.4 Hz, 1H), 6.10 (d, J = 2.4 Hz, 1H), 5.49 (br s, 1H),
5.06 (s, 1H), 3.90 (s, 6H), 3.83 (s, 3H), 3.78 (s, 3H), 3.76 (s, 3H), 3.07 (dd,
Jgem = 17.9 Hz, J = 4.4 Hz, 1H), 3.00 (d, Jgem = 17.9 Hz, J = 2.4 Hz, 1H);
FT-IR (solid) 3341, 2917, 2851, 1709, 1618, 1594, 1513, 1499, 1462, 1426, 1362,
1338, 1260, 1216, 1203, 1145, 1113, 1052, 958, 816, 759, 720, 615 cm-1;
HRMS (ESI-TOF) calcd for C27H29O11 [M+H]+
529.1710, found 529.1699
5,7,3’,5’-O-Tetramethyl-epigallocatechin-3-gallate (57)
Yield 55%; TLC Rf 0.49 (CHCl3/methanol = 9/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.90 (s, 2H), 6.75 (s, 2H), 6.05 (d, J = 2.4 Hz, 1H), 6.01 (d, J = 1.9 Hz, 1H),
5.46 (br s, 1H), 5.09 (s, 1H), 3.90 (s, 3H), 3.80 (s, 3H), 3.79 (s, 6H), 2.99
(dd, Jgem = 17.4 Hz, J = 3.9 Hz, 1H), 2.83 (d, Jgem = 17.4 Hz, 1H); FT-IR
(solid) 3230, 2924, 2851, 1693, 1594, 1511, 1442, 1371, 1345, 1224, 1189, 1144,
1116, 1039, 823, 764, 721, 510 cm-1; HRMS (ESI-TOF) calcd for C26H27O11
[M+H]+ 515.1553, found 515.1569.
5,7,3’,5’,4”-O-Pentamethyl-epigallocatechin-3-gallate (58)
Yield 51%; TLC Rf 0.61 (CHCl3/methanol =
9/1); 1H NMR (400 MHz, CDCl3) δ 7.13 (s, 2H), 6.72 (s,
2H), 6.25 (d, J = 1.9 Hz, 1H), 6.12 (d, J = 1.9 Hz, 1H), 5.58 (br s, 1H), 5.05
(s, 1H), 3.91 (s, 3H), 3.81 (s, 3H), 3.80 (s, 6H), 3.78 (s, 3H), 3.03 (br d, J =
2.9 Hz, 2H); FTIR (solid) 3387, 2925, 2849, 1713, 1620, 1591, 1505, 1460, 1421,
1365, 1344, 1219, 1201, 1147, 1120, 1048, 1001, 948, 872, 814, 759, 732, 718,
669 cm-1; HRMS (ESI-TOF) calcd for C27H32NO11
[M+H]+ 546.1975, found 546.1987.
5,7,3’,5’,3”,4”-O-Hexamethyl-epigallocatechin-3-gallate
(59)
Yield 57%; TLC Rf 0.55 (CHCl3/methanol
= 12/1); 1H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 1.9 Hz,
1H), 7.09 (d, J = 1.9 Hz, 1H), 6.72 (s, 2H), 6.25 (d, J = 2.4 Hz, 1H), 6.11 (d,
J = 2.4 Hz, 1H), 5.59 (br s, 1H), 5.05 (s, 1H), 3.92 (s, 3H), 3.84 (s, 3H),
3.81 (s, 3H), 3.78 (s, 3H), 3.78 (s, 6H), 3.04 (d, J = 3.4 Hz, 2H, l); 13C
NMR (67.8 MHz, CDCl3) δ 165.1, 159.6, 158.8, 155.5, 151.9, 148.6,
146.8, 139.5, 134.4, 128.9, 125.4, 109.8, 106.0, 103.4, 100.0, 93.4, 92.0,
77.9, 77.2, 68.8, 61.0, 56.1, 56.0, 55.4x2, 25.9; FT-IR (solid) 3394, 2919,
2849, 1709, 1618, 1592, 1499, 1460, 1427, 1361, 1344, 1217, 1202, 1146, 1111,
1045, 996, 982, 947, 818, 759, 717, 664, 532 cm-1; HRMS (ESI-TOF)
calcd for C28H31O11 [M+H]+ 543.1866, found
543.1881.
5,7,3’,5’,3”,5”-O-Hexamethyl-epigallocatechin-3-gallate
(60)
Yield 53%; TLC Rf 0.55 (CHCl3/methanol
= 12/1); 1H NMR (400 MHz, CDCl3) δ 7.20 (s, 2H), 6.70 (s, 2H), 6.25
(d, J = 1.9 Hz, 1H), 6.12 (d, J = 1.9 Hz, 1H), 5.66 (br s, 1H), 5.07 (s, 1H),
3.85 (s, 6H), 3.80 (s, 3H), 3.79 (s, 3H), 3.73 (s, 6H) 3.06 (dd, Jgem = 16.9
Hz, J = 4.3 Hz, 1H), 2.99 (d, Jgem = 16.9 Hz, J = 2.9 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 165.2, 159.7, 158.9, 155.6, 146.9, 146.5,
139.4, 134.6, 128.9, 121.1, 107.0, 103.6, 100.2, 93.3, 91.9, 77.9, 77.2, 68.5,
56.4, 56.2, 55.4x2, 26.0; FT-IR (solid) 3401, 2942, 2839, 1703, 1612, 1592,
1514, 1498, 1454, 1422, 1355, 1325, 1202, 1144, 1145, 1111, 1033, 962, 910,
868, 817, 756, 739, 587 cm-1; HRMS (ESI-TOF) calcd for C28H31O11
[M+H]+ 543.1866, found 543.1885.
5,7,3’,4’,5’-O-Pentamethyl-epigallocatechin-3-gallate (61)
Yield 43%; TLC Rf 0.24 (CHCl3/methanol = 12/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ
6.96 (s, 2H), 6.84 (s, 2H), 6.14 (d, J = 2.4 Hz, 1H), 6.11 (d, J = 2.4 Hz, 1H),
5.49 (br s, 1H), 5.16 (s, 1H), 3.71 (s, 3H), 3.71 (s, 3H), 3.67 (s, 6H), 3.61
(s, 3H), 3.00 (dd, Jgem = 17.9 Hz, J = 4.4 Hz, 1H), 2.84 (d, Jgem = 17.9 Hz,
1H); 13C NMR (67.8 MHz, acetone-d6/D2O = 2/1) δ 165.9, 159.4, 158.7, 155.2, 152.8, 144.5, 133.4, 109.1,
109.6, 104.7, 99.7, 95.1, 93.6, 78.1, 69.2, 60.5, 56.1, 55.3x2, 26.3; FT-IR
(solid) 3338, 1691, 1592, 1498, 1453, 1420, 1306, 1191, 1145, 1119, 1035, 972,
813, 758, 631, 461 cm-1; HRMS (ESI-TOF) calcd for C27H32NO11
[M+NH4]+ 546.1975, found 546.1995.
5,7,3’,4’,5’,4”-O-Hexamethyl-epigallocatechin-3-gallate
(62)
Yield 55%; TLC Rf 0.34 (CHCl3/methanol
= 12/1); 1H NMR (400 MHz, acetone-d6/D2O =
2/1) δ 6.91 (s, 2H), 6.83 (s, 2H), 6.14 (d, J = 2.4 Hz, 1H), 6.11 (d, J = 2.4
Hz, 1H), 5.51 (br s, 1H), 5.17 (s, 1H), 3.76 (s, 3H), 3.71 (s, 3H), 3.70 (s,
3H), 3.66 (s, 6H), 3.60 (s, 3H), 3.00 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H),
2.85 (d, Jgem = 17.9 Hz, 1H); 13C NMR (100 MHz, acetone-d6/D2O
= 2/1) δ 165.5, 159.2, 155.9, 155.7, 153.0, 148.6, 138.6, 137.6, 133.4, 125.7,
109.8, 103.8, 100.0, 93.4, 92.1, 77.9, 68.8, 60.9, 60.8, 56.0, 55.4x2, 25.9;
FT-IR (solid) 3379, 1707, 1618, 1591, 1499, 1454, 1420, 1345, 1219, 1194, 1145,
1116, 1053, 998, 975, 873, 838, 814, 759, 733, 712, 670, 631 cm-1;
HRMS (ESI-TOF) calcd for C28H31O11 [M+H]+ 543.1866,
found 543.1891.
5,7,3’,4’,5’,3”,4”-O-Heptamethyl-epigallocatechin-3-gallate
(63)
Yield 59%; TLC Rf 0.66 (CHCl3/methanol =
15/1); 1H NMR (400 MHz, CDCl3)δ
7.26 (d, J = 1.4 Hz, 1H), 7.09
(d, J = 1.4 Hz, 1H), 6.72 (s, 2H), 6.25 (d, J = 2.4 Hz, 1H), 6.12 (d, J = 2.4 Hz,
1H), 5.61 (br s, 1H), 5.06 (s, 1H), 3.92 (s, 3H), 3.84 (s, 3H), 3.81 (s, 3H),
3.80 (s, 3H), 3.78 (s, 3H), 3.76 (s, 6H), 3.04 (d, J = 3.4 Hz, 2H); FT-IR
(solid) 3386, 1710, 1619, 1589, 1503, 1455, 1420, 1362, 1342, 1216, 1196, 1145,
1120, 1048, 999, 982, 948, 872, 814, 758, 734, 717, 667, 631 cm-1;
HRMS (ESI-TOF) calcd for C29H36NO11 [M+NH4]+
574.2288, found 574.2317.
5,7,3’,4’,5’,3”,5”-O-Heptamethyl-epigallocatechin-3-gallate
(64)
Yield 68%; TLC Rf 0.66 (CHCl3/methanol =
15/1); 1H NMR (400 MHz, CDCl3) δ 7.20 (s, 2H), 6.70 (s,
2H), 6.25 (d, J = 2.4 Hz, 1H), 6.12 (d, J = 2.4 Hz, 1H), 5.66 (br s, 1H), 5.09
(s, 1H), 3.85 (s, 3H), 3.85 (s, 3H), 3.80 (s, 6H), 3.79 (s, 3H), 3.71 (s, 6H),
3.05 (br s, 1H), 3.04 (br s, 1H); 13C NMR (67.8 MHz, CDCl3)
d 165.3, 159.8, 158.9, 155.6, 153.2, 146.7, 139.5, 137.9, 133.5, 121.0, 107.0,
104.0, 100.3, 93.3, 91.9, 77.9, 68.5, 60.8, 56.5, 56.5, 56.1, 55.4, 26.0; FTIR
(solid) 3387, 1707, 1618, 1591, 1498, 1453, 1420, 1356, 1329, 1203, 1183, 1145,
1114, 1035, 1005, 954, 915, 816, 758, 717, 668, 633 cm-1; HRMS
(ESI-TOF) calcd for C29H33O11 [M+H]+ 557.2023, found
557.2022.
(2R*,3R*)-2-[3,4,5-Tris(benzyloxy)phenyl]-5,7-bis(4-fluorobenzyloxy)chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-1)
TLC Rf 0.44 (hexane/ethyl acetate = 2/1); 1H
NMR (400 MHz, CDCl3) δ 7.19-7.39 (m, 36H, aromatic), 7.01-7.07 (m,
4H, aromatic), 6.73 (s, 2H), 6.38 (d, J = 1.9 Hz, 1H), 6.30 (d, J = 1.9 Hz,
1H), 5.66 (br s, 1H), 5.04 (s, 1H), 4.66-5.01 (m, 16H, Bn), 3.10 (dd, Jgem =
17.9 Hz, J = 4.3 Hz, 1H), 3.03 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H, f); 13C
NMR (100 MHz, CDCl3) δ 164.9, 162.7 (JC,F = 247 Hz),
162.6 (JC,F = 247 Hz), 158.8, 158.0, 155.8, 153.0, 152.5, 142.9,
138.6, 137.8, 137.5, 137.0, 136.5, 136.2, 133.2, 132.6 (JC,F = 3.0
Hz), 132.5 (JC,F = 3.0 Hz), 129.4 (JC,F = 8.4 Hz), 129.1
(JC,F = 8.4 Hz), 128.6x2, 128.5, 128.4, 128.3, 128.2x2, 128.0,
127.9, 127.8, 127.6x2, 125.0, 115.6 (JC,F = 21.8 Hz), 109.3, 106.9,
101.2, 94.8, 94.1, 78.1, 75.2, 75.1, 71.3, 71.2, 69.6, 69.5, 68.3, 26.3; FT-IR
(solid) 3033, 2927, 1716, 1616, 1593, 1512, 1455, 1430, 1372, 1227, 1114, 911,
826, 752, 697, 504 cm-1; HRMS (ESI-TOF) calcd for C78H64F2O11
[M+H]+ 1215.4495, found 1215.4495.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-2)
Yield 54%; TLC Rf 0.43 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.19-7.39 (m,
31H,aromatic), 6.99-7.07 (m, 4H, aromatic), 6.71 (s, 2H), 6.39(d, J = 1.9 Hz,
1H), 6.30 (d, J = 1.9 Hz,1H), 5.65 (br s, 1H), 4.94-5.03 (m, 11H), 4.74 (d, J =
11.6 Hz, 2H), 4.62 (d, J = 11.6 Hz, 2H), 3.77 (s, 3H), 3.09 (dd, Jgem = 17.9
Hz, J = 4.3 Hz, 1H), 3.03 (dd, Jgem = 17.9 Hz, J = 1.9Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 164.8, 162.6x2 (1JC,F =
247 Hz), 158.8, 158.0, 155.8, 153.0, 152.1,143.9, 138.6, 137.8, 137.0, 136.6,
136.5, 133.2, 132.6 (4JC,F = 2.3 Hz), 129.4 (3JC,F
= 8.4 Hz), 129.1 (3JC,F = 8.4 Hz), 128.7, 128.6, 128.5, 128.4,
128.3x2, 128.2, 127.8x2, 127.7, 127.6x2, 127.5, 124.7, 115.6 (2JC,F
=22.1 Hz), 109.3, 106.9, 101.2, 94.8, 94.1, 78.1, 75.2, 71.3, 71.1, 69.6, 69.5,
68.2, 60.9, 26.4.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-3)
Yield 56%; TLC Rf 0.36 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.18-7.38 (m, 26H,
aromatic), 7.04x2 (t, J = 8.7 Hz, 4H), 6.74 (s, 2H, c), 6.35(d, J = 2.4 Hz,
1H), 6.28 (d, J = 2.4 Hz, 1H), 5.65 (br s, 1H), 5.07 (s, 1H), 4.93-5.05 (m,
8H), 4.84 (d, J = 11.6 Hz, 2H), 4.71 (d, J = 11.6 Hz, 2H), 3.78 (s, 3H), 3.77
(s, 3H), 3.11 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.04 (dd, Jgem = 17.9 Hz, J
= 1.9 Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 165.0, 162.6x2
(1JC,F = 247 Hz), 158.8, 158.0, 155.8, 153.3, 153.0,
151.8, 143.3, 137.8, 137.0, 136.5, 133.3, 132.6 (4JC,F =
1.7 Hz), 129.4 (3JC,F = 8.4 Hz), 129.1 (3JC,F = 8.4 Hz),
128.7, 128.6, 128.5, 128.2, 128.0, 127.9, 127.8, 127.6, 127.5, 124.9, 115.6x2 (2JC,F
=22.1 Hz), 109.2, 107.5, 106.9, 101.2, 94.8, 94.7, 78.0, 75.2, 71.4, 71.1,
69.6, 68.4, 60.9, 56.4, 26.3.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-4)
Yield 43%; TLC Rf 0.39 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.19-7.42 (m, 26H,
aromatic), 7.08 (t, J = 8.7 Hz, 2H), 7.05 (t, J = 8.7 Hz, 2H), 6.80 (s, 2H, c),
6.31 (d, J = 1.9 Hz, 1H), 6.25 (d, J = 1.9 Hz, 1H), 5.63 (br s, 1H), 5.07 (s,
1H), 4.93-5.02 (m, 10H), 4.85 (d, J = 11.6 Hz, 2H), 3.76 (s, 6H), 3.11 (dd, Jgem
= 17.9 Hz, J = 4.3 Hz, 1H), 3.06 (dd, Jgem = 17.9 Hz, J = 2.9 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 165.2, 164.4, 158.7, 157.9, 155.7, 153.3,
153.0, 141.7, 138.7, 137.5, 137.0, 133.4, 132.7 (4JC,F =
3.4 Hz), 132.6 (4JC,F = 3.9 Hz), 129.4 (3JC,F
= 7.8 Hz), 129.1 (3JC,F = 7.8 Hz), 128.6, 128.5, 128.3,
128.2, 128.0x2, 127.9, 127.6, 127.5, 125.2, 115.6x2 (2JC,F
=21.8 Hz), 107.4, 107.0, 101.1, 94.8, 94.0, 77.8, 75.3, 75.0, 71.6, 69.6, 69.5,
68.7, 56.4, 26.3.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-5)
Yield 41%; TLC Rf 0.46 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.22-7.37 (m, 31H,
aromatic), 7.04 (t, J = 8.7 Hz, 2H), 7.02 (t, J = 8.7 Hz, 2H), 6.71 (s, 2H),
6.36 (d, J = 1.9 Hz, 1H), 6.29 (d, J = 1.9 Hz, 1H), 5.63 (br s, 1H, f), 5.05
(s, 1H), 4.92-5.03 (m, 10H), 4.82 (d, J = 11.6 Hz, 2H), 4.71 (d, J = 11.6 Hz,
2H), 3.80 (s, 3H), 3.09 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H, i), 3.02 (dd, Jgem
= 17.9 Hz, J = 2.4Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ
164.3, 158.7, 157.9, 155.7, 152.6, 152.4, 142.8, 139.5, 137.4, 136.9, 136.4,
132.9, 132.5 (3JC,F = 3.4 Hz),, 129.3 (3JC,F
= 7.8 Hz), 129.0 (3JC,F = 7.8 Hz), 128.5x2, 128.4, 128.3,
128.2, 128.1, 127.9, 127.8, 127.4x2, 127.3, 124.8, 115.5 (2JC,F
=21.8 Hz), 109.2, 106.9, 101.1, 94.7, 94.0, 77.9, 75.0, 71.2, 71.1, 69.5, 69.4,
68.2, 60.9, 26.2.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-6)
Yield 58%; TLC Rf 0.41 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.21-7.38 (m, 26H,
aromatic), 7.04 (t, J = 8.7 Hz, 2H), 7.02 (t, J = 8.7 Hz, 2H), 6.68 (s, 2H),
6.36 (d, J = 1.4 Hz, 1H), 6.29 (d, J = 1.4 Hz, 1H), 5.63 (br s, 1H), 5.05 (s,
1H), 4.98-5.02 (m, 8H), 4.77 (d, J = 11.6 Hz, 2H), 4.66 (d, J = 11.6 Hz, 2H),
3.80 (s, 3H), 3.78 (s, 3H), 3.08 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.01
(dd, Jgem = 17.9 Hz, J = 1.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 164.8, 162.5 (1JC,F = 246 Hz), 158.7, 158.0, 155.8,
152.7, 152.1, 143.9, 139.7, 137.0, 136.5, 132.9, 132.6 (4JC,F
= 2.8 Hz ), 129.4 (3JC,F = 8.4 Hz), 129.1 (3JC,F
= 7.8 Hz), 128.7, 128.5x2, 128.2, 127.9, 127.8, 127.6, 127.5, 127.4, 124.7,
115.6 (2JC,F =21.8 Hz), 109.3, 107.0, 101.2, 94.8, 94.0,
78.1, 71.2, 71.1, 69.6, 69.4, 68.2, 60.9, 26.4.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-7)
Yield 57%; TLC Rf 0.32 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.27-7.39 (m, 21H,
aromatic), 7.04 (br t, J = 8.7 Hz, 4H), 6.72 (s, 2H), 6.33 (d, J = 1.9 Hz, 1H),
6.27 (d, J = 1.9 Hz, 1H), 5.63 (br s, 1H), 5.00 (s, 1H), 4.98-5.04 (m, 6H),
4.86 (d, J = 11.6 Hz, 2H), 4.74 (d, J = 11.6 Hz, 2H), 3.81 (s, 3H), 3.78 (s,
6H), 3.09 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.02 (dd, Jgem = 17.9 Hz, J =
2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 165.0, 161.4,
158.8, 158.0, 155.8, 153.3,152.7, 151.8, 143.3, 139.8, 137.0, 136.5, 133.0,
132.6, 129.4 (3JC,F = 7.6 Hz), 129.1 (3JC,F
= 7.6 Hz), 128.7, 128.5, 128.2, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4,
124.9, 115.7 (2JC,F =22.1 Hz), 115.5 (2JC,F
=21.3 Hz), 109.2, 107.5, 107.1, 101.2, 94.8, 94.1, 77.9, 77.6, 71.4, 71.1,
69.5x2, 68.4, 61.0, 56.4, 56.3, 25.7.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-8)
Yield 57%; TLC Rf 0.36 (hexane/ethyl acetate
= 2/1); 1H NMR (270 MHz, CDCl3) d 7.29-7.42 (m, 19H,
aromatic), 7.18 (s, 2H), 7.07 (t, J = 8.6 Hz, 2H7.04 (t, J = 8.6 Hz, 2H), 6.78
(s, 2H), 6.29 (d, J = 1.9 Hz, 1H), 6.25 (d, J = 1.9 Hz, 1H), 5.61 (br s, 1H), 5.04
(s, 1H), 4.86-5.02 (m, 10H), 3.83 (s, 3H), 3.76 (s, 6H), 3.10 (dd, Jgem = 17.9
Hz, J = 4.4 Hz, 1H), 3.04 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) d 165.3, 162.6x2 (1JC,F
= 247 Hz), 158.7, 157.9, 155.7, 153.3, 152.7, 141.7, 139.8, 137.4, 137.0,
133.1, 132.7, 132.6 (4JC,F = 3.4 Hz), 129.4 (3JC,F
= 7.8 Hz), 129.1 (3JC,F = 8.4 Hz), 128.6, 128.4, 128.3x2,
128.0x2, 127.5, 127.4, 125.2, 115.6x2 (2JC,F =21.8 Hz),
107.4, 107.1, 101.1, 94.8, 94.0, 77.7, 75.0, 71.5, 69.6, 69.4, 68.6, 61.0, 56.4,
26.0.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-9)
Yield 52%; TLC Rf 0.42 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.26-7.43 (m, 26H,
aromatic), 7.05 (t, J = 8.7 Hz, 2H), 7.03 (t, J = 8.7 Hz, 2H), 6.60 (s, 2H),
6.40 (d, J = 1.9 Hz, 1H), 6.29 (d, J = 1.9 Hz, 1H), 5.66 (br s, 1H), 4.93-5.08
(m, 13H), 3.50 (s, 6H), 3.11 (dd, Jgem = 17.4 Hz, J = 4.3 Hz, 1H), 3.05 (dd, Jgem
= 17.4 Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ
164.8, 162.5 (1JC,F = 247 Hz), 158.7, 157.9, 155.7,
153.5, 152.3, 142.5, 137.7, 137.3, 137.0, 136.5, 133.4, 132.5, 129.3 (3JC,F
= 8.4 Hz), 129.0 (3JC,F = 8.4 Hz), 128.6, 128.5, 128.4,
128.2, 128.1, 128.0, 127.8, 127.6, 124.9, 115.5 (2JC,F
=21.8 Hz), 109.2, 104.2, 101.1, 94.7, 94.0, 78.1, 75.1, 74.9, 71.1, 69.5, 69.4,
68.3, 55.9, 26.3.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-10)
Yield 56%; TLC Rf 0.41 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.27-7.42 (m, 21H,
aromatic), 7.12 (t, J = 8.7 Hz, 2H), 7.03 (t, J = 8.7 Hz, 2H), 6.60 (s, 2H),
6.41 (d, J = 1.9 Hz, 1H), 6.30 (d, J = 1.9 Hz, 1H), 5.66 (br s, 1H), 4.92-5.07
(m, 11H), 3.89 (s, 3H, h), 3.50 (s, 6H), 3.11 (dd, Jgem = 17.9 Hz, J = 4.8 Hz,
1H), 3.04 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 164.9, 160.8, 158.8, 158.0, 155.8, 153.6, 152.3, 152.1, 144.0, 137.8, 137.1,
136.6, 133.3, 132.6, 129.4 (3JC,F = 8.4 Hz), 129.3 (3JC,F
= 8.4 Hz), 128.7, 128.5, 128.2, 127.8x2, 127.6, 124.8, 115.6 (2JC,F
=21.8 Hz), 110.4, 109.5, 104.2, 101.2, 94.9, 94.1, 78.2, 75.0, 71.2, 69.6,
69.5, 68.3, 61.1, 56.0, 26.4.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-11)
Yield 47%; TLC Rf 0.35 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.16-7.43 (m, 16H,
aromatic), 7.04 (br t, J = 8.7 Hz, 4H), 6.63 (s, 2H), 6.38 (d, J = 1.9 Hz, 1H),
6.28 (d, J = 1.9 Hz, 1H), 5.67 (br s, 1H, f), 4.93-5.06 (m, 9H), 3.88 (s, 3H),
3.81 (s, 3H), 3.57 (s, 6H, j), 3.12 (dd, Jgem = 17.9 Hz, J = 4.9 Hz, 1H), 3.05
(dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 165.0, 164.4, 158.8, 158.0, 155.8, 153.6, 153.2, 151.9, 144.1, 143.4, 137.8,
137.1, 136.6, 133.4, 132.6, 129.4 (3JC,F = 8.4 Hz), 129.1
(3JC,F = 7.8 Hz), 128.7x2, 128.5, 128.2x2, 127.9, 124.9,
115.6 (2JC,F =22.9 Hz), 109.3, 107.5, 104.2, 101.2, 94.9,
94.1, 78.1, 75.1, 71.2, 69.6, 69.5, 68.5, 61.0, 56.4, 56.1, 26.3.
(2R*,3R*)-5,7-Bis4-fluorobenzyloxy)-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-12)
Yield 55%; TLC Rf 0.37 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.28-7.43 (m, 14H,
aromatic), 7.16 (s, 2H), 7.03-7.10 (m, 4H, aromatic), 6.67 (s, 2H), 6.33 (d, J =
1.9 Hz, 1H), 6.25 (d, J = 1.9 Hz, 1H), 5.66 (br s, 1H), 5.08 (s, 1H), 5.05 (s,
2H, Bn), 5.00 (s, 2H, Bn), 4.98 (s, 2H, Bn), 4.95 (s, 2H, Bn), 3.78 (s, 6H),
3.65 (s, 6H), 3.12 (dd, Jgem = 17.9 Hz, J = 4.8 Hz, 1H), 3.06 (d, Jgem = 17.9
Hz, 1H); FT-IR (neat) 2939, 1715, 1618, 1592, 1512, 1463, 1417, 1360, 1333,
1225, 1183, 1149, 1128, 1039, 826, 756, 734, 698 cm-1.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-13)
Yield 48%; TLC Rf 0.38 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.26-7.36 (m, 21H,
aromatic), 7.00-7.06 (m, 4H, aromatic), 6.60 (s, 2H), 6.39 (d, J = 1.9 Hz, 1H),
6.30 (d, J = 1.9 Hz, 1H), 5.66 (br s, 1H), 4.98-5.08 (m, 11H), 3.78 (s, 3H),
3.52 (s, 6H), 3.11 (dd, Jgem = 17.4 Hz, J = 3.9 Hz, 1H), 3.04 (dd, Jgem = 17.4
Hz, J = 1.4 Hz, 1H).
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-14)
Yield 53%; TLC Rf 0.36 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.28-7.40 (m, 16H,
aromatic), 7.04 (t, J = 8.7 Hz, 2H), 7.02 (t, J = 8.7 Hz, 2H), 6.60 (s, 2H),
6.40 (d, J = 1.9 Hz, 1H), 6.30 (d, J = 1.9 Hz, 1H), 5.67 (br s, 1H), 5.02 (s,
1H), 4.99-5.06 (m, 8H, Bn), 3.89 (s, 3H), 3.78 (s, 3H), 3.53 (s, 6H), 3.11 (dd,
Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.05 (dd, Jgem = 17.9 Hz, J = 1.4 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 164.9, 162.6, 158.8, 158.0, 155.8, 153.2,
152.1, 144.0, 140.5, 138.1, 136.6, 133.1, 132.6, 129.4 (3JC,F
= 8.4 Hz), 129.1 (3JC,F = 8.4 Hz), 128.7, 128.2, 127.8,
124.8, 115.6 (2JC,F =21.8 Hz), 109.4, 104.1, 101.2, 94.8,
94.1, 78.2, 71.1, 69.6, 69.5, 68.3, 61.1, 60.9, 56.0, 26.4.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-15)
Yield 49%; TLC Rf 0.30 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.26-7.40 (m, 11H,
aromatic), 7.04 (t, J = 8.7 Hz, 4H), 6.64 (s, 2H), 6.38 (d, J = 2.4 Hz, 1H),
6.28 (d, J = 2.4 Hz, 1H), 5.67 (br s, 1H), 4.99-5.08 (m, 7H), 3.88 (s, 3H),
3.81 (s, 3H), 3.79 (s, 3H), 3.60 (s, 6H), 3.12 (dd, Jgem = 17.9 Hz, J = 4.3 Hz,
1H), 3.06 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 165.0, 160.7, 158.7, 158.0, 155.8, 153.2, 151.8, 143.3, 138.0, 136.5, 133.2,
132.6 (4JC,F = 2.2 Hz), 132.5 (4JC,F
= 2.2 Hz), 129.4 (3JC,F = 8.4 Hz), 129.1 (3JC,F
= 8.4 Hz), 128.7, 128.3, 127.9, 124.9, 115.6x2 (2JC,F
=21.2 Hz), 109.2, 107.5, 104.1, 101.2, 94.8, 94.1, 78.1, 71.1, 69.6, 69.5,
68.4, 61.0, 60.9, 56.4, 56.0, 26.4.
(2R*,3R*)-5,7-Bis(4-fluorobenzyloxy)-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-16)
Yield 50%; TLC Rf 0.31 (hexane/ethyl acetate
= 2/1); 1H NMR (400 MHz, CDCl3) δ 7.28-7.44 (m, 9H,
aromatic), 7.16 (s, 2H), 7.08 (t, J = 8.7 Hz, 2H), 7.04 (t, J = 8.7 Hz, 2H),
6.68 (s, 2H, d), 6.33 (d, J = 2.4 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H), 5.66 (br
s, 1H), 5.08 (s, 1H), 5.05 (s, 2H, Bn), 5.00 (s, 2H, Bn), 4.98 (s, 2H, Bn),
3.80 (s, 3H), 3.78 (s, 6H), 3.69 (s, 6H), 3.12 (dd, Jgem = 18.4 Hz, J = 4.8 Hz,
1H), 3.06 (dd, Jgem = 18.4 Hz, J = 2.9 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 165.2, 162.6 (1JC,F = 247 Hz), 162.5 (1JC,F
= 247 Hz), 158.7, 157.9, 155.8, 153.3x2, 141.5, 138.1, 137.3, 133.3, 132.6 (4JC,F
= 1.7 Hz), 132.5 (4JC,F = 1.7 Hz), 129.4 (3JC,F
= 7.8 Hz), 129.1 (3JC,F = 7.8 Hz), 128.5, 128.3, 128.1,
125.2, 115.6x2 (2JC,F = 21.8 Hz), 107.4, 104.1, 101.1,
94.8, 94.0, 78.0, 69.6, 69.5, 68.6, 60.9, 56.4, 56.1, 26.2; FT-IR (neat) 3010,
2939, 2841, 1715, 1621, 1593, 1512, 1463, 1417, 1361, 1334, 1228, 1183, 1149,
1129, 1040, 1014, 827, 756, 699, 506 cm-1.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-17)
Yield 40%; TLC Rf 0.68 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.19-7.42 (m, 37H,
aromatic), 6.73 (s, 2H), 6.38 (d, J = 1.9 Hz, 1H), 6.30 (d, J = 1.9 Hz, 1H),
5.66 (br s, 1H), 4.95-5.04 (m, 9H), 4.90 (s, 2H, Bn), 4.80 (d, Jgem = 11.6 Hz,
2H), 4.67 (d, Jgem = 11.6 Hz, 2H), 3.80 (s, 3H), 3.10 (dd, Jgem = 17.9 Hz, J =
4.3 Hz, 1H), 3.03 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C NMR
(67.8 MHz, CDCl3) δ 164.8, 158.9x2, 155.5, 152,8, 152.3, 142.7,
138.4, 137.7, 137.4, 136.8x2, 136.4, 133.3, 128.6, 128.5, 128.4x2, 128.3,
128.2, 128.1, 128.0x3, 127.8, 127.7, 127.5x2, 127.4, 124.9, 109.1, 106.6,
100.5, 94.2, 92.7, 77.9, 75.1, 75.0, 71.1, 71.0, 70.1, 68.2, 55.4, 26.0; HRMS
(ESI-TOF) calcd for C72H66NO11 [M+NH4]+
1120.4636, found 1120.4679.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-18)
Yield 38%; TLC Rf 0.66 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.19-7.41 (m, 32H,
aromatic), 6.71 (s, 2H), 6.38(d, J = 2.4 Hz, 1H), 6.26 (d, J = 2.4 Hz, 1H),
5.65 (br s, 1H), 4.94-5.06 (m, 9H), 4.75 (d, Jgem = 11.6 Hz, 2H), 4.62 (d, Jgem
= 11.6 Hz, 2H, Bn), 3.80 (s, 3H), 3.77 (s, 3H), 3.05 (dd, Jgem = 17.9 Hz, J =
4.3 Hz, 1H), 2.98 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C NMR
(67.8 MHz, CDCl3) δ 164.8, 159.1, 159.0, 155.6, 152,9, 152.1, 143.7,
138.5, 137.8, 137.0, 136.9, 136.5, 133.3, 128.7, 128.6, 128.4, 128.1x2, 127.8x2,
127.6x3, 127.5, 124.8, 109.2, 106.7, 100.6, 94.3, 92.8, 78.0, 75.2, 71.2, 71.0,
70.2, 68.3, 60.9, 55.5, 26.2; FT-IR (neat) 2964, 1716, 1621, 1591, 1496, 1427,
1370, 1261, 1213, 1102, 1047, 801, 736, 697 cm-1; HRMS (ESI-TOF)
calcd for C66H62NO11 [M+NH4]+
1044.4323, found 1044.4332.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-19)
Yield 39%; TLC Rf 0.61 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.17-7.43 (m, 27H,
aromatic), 6.75 (s, 2H), 6.35 (d, J = 2.4 Hz, 1H), 6.24 (d, J = 2.4 Hz, 1H),
5.65 (br s, 1H), 4.96-5.14 (m, 7H), 4.84 (d, Jgem = 11.6 Hz, 2H), 4.71 (d, Jgem
= 11.6 Hz, 2H), 3.79 (s, 3H), 3.77 (s, 3H), 3.77 (s, 3H), 3.07 (dd, Jgem = 17.9
Hz, J = 4.3 Hz, 1H), 3.03 (dd, Jgem = 17.9 Hz, J = 3.4 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 165.0, 159.0x2, 155.5, 153,2, 152.9, 151.8,
137.8, 137.0, 136.9, 136.5, 133.4, 128.7, 128.6, 128.5, 128.4, 128.2x2, 128.1,
128.0, 127.9x2, 127.8, 127.6x3, 127.5, 124.9, 109.1, 107.3, 106.8, 100.5, 94.3,
92.8, 77.9, 75.2, 71.3, 71.0, 70.2, 68.5, 60.9, 56.3, 55.5, 26.1; HRMS
(ESI-TOF) calcd for C60H58NO11 [M+NH4]+
968.4010, found 968.4053.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-20)
Yield 41%; TLC Rf 0.63 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ d 7.18-7.45 (m, 27H,
aromatic), 6.80 (s, 2H), 6.30(d, J = 2.4 Hz, 1H), 6.21 (d, J = 2.4 Hz, 1H,),
5.63 (br s, 1H), 4.84-5.06 (m, 11H), 3.78 (s, 3H), 3.75 (s, 6H), 3.06 (dd, Jgem
= 17.9 Hz, J = 4.3 Hz, 1H), 3.02 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 165.3, 159.0, 155.5, 153,3, 152.9, 141.5,
138.5, 137.8, 137.4, 137.0x2, 133.5, 128.7, 128.6, 128.5, 128.3x2, 128.2,
128.1, 128.0, 127.9, 127.8, 127.6x2, 127.5, 125.3, 107.3, 106.9, 100.5, 92.8,
77.0, 75.2, 75.0, 71.5, 70.2, 68.7, 56.4, 55.5, 25.9; HRMS (ESI-TOF) calcd for
C60H58NO11 [M+NH4]+ 968.4010, found
968.4009.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-21)
Yield 44%; TLC Rf 0.66 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.41 (m, 32H,
aromatic), 6.71 (s, 2H), 6.35 (d, J = 1.9 Hz, 1H), 6.25 (d, J = 1.9 Hz, 1H),
5.63 (br s, 1H), 5.04 (s, 1H, e), 4.91-5.03 (m, 8H, Bn), 4.82 (d, Jgem = 11.6
Hz, 2H, Bn), 4.71 (d, Jgem = 11.6 Hz, 2H, Bn), 3.80 (s, 3H), 3.80 (s, 3H), 3.04
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.98 (dd, Jgem = 17.9 Hz, J = 2.4 Hz,
1H); 13C NMR (67.8 MHz, CDCl3) δ 164.9, 159.0x2, 155.6,
152,7, 152.4, 142.8, 139.6, 137.5, 137.0, 136.9, 136.5, 133.1, 128.7, 128.6,
128.5, 128.3, 128.2, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5, 127.4, 125.0,
109.2, 106.9, 100.6, 94.3, 92.8, 77.9, 75.1, 71.2, 71.1, 70.2, 68.3, 60.9,
55.5, 26.1; HRMS (ESI-TOF) calcd for C66H62NO11
[M+NH4]+ 1044.4323, found 1044.4333.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-22)
Yield 49%; TLC Rf 0.64 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.46 (m, 27H,
aromatic), 6.69 (s, 2H), 6.36 (d, J = 2.4 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H),
5.63 (br s, 1H), 5.06 (s, 1H), 4.99-5.03 (m, 6H), 4.77 (d, Jgem = 11.6 Hz, 2H),
4.65 (d, Jgem = 11.6 Hz, 2H), 3.80 (s, 3H), 3.80 (s, 3H), 3.78 (s, 3H), 3.03
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.97 (dd, Jgem = 17.9 Hz, J = 2.4 Hz,
1H); 13C NMR (67.8 MHz, CDCl3) δ 164.8, 159.1x2, 155.6,
152,7, 152.1, 143.9, 139.7, 137.1, 136.9, 136.6, 133.1, 128.7, 128.5x2, 128.1,
127.8x2, 127.6, 127.5x2, 127.4, 124.8, 109.4, 107.0, 100.6, 94.4, 92.9, 78.0,
71.3, 71.1, 70.3, 68.3, 60.9, 55.5, 26.1; HRMS (ESI-TOF) calcd for C60H58NO11
[M+NH4]+ 968.4010, found 968.4009.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-23)
Yield 45%; TLC Rf 0.57 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.17-7.42 (m, 22H,
aromatic), 6.72 (s, 2H), 6.33 (d, J = 2.4 Hz, 1H), 6.23 (d, J = 2.4 Hz, 1H,),
5.63 (br s, 1H), 5.01-5.03 (m, 4H, Bn), 5.00 (s, 1H), 4.86 (d, Jgem = 11.6 Hz,
2H, Bn), 4.74 (d, Jgem = 11.6 Hz, 2H, Bn), 3.81(s, 3H), 3.79 (s, 3H), 3.78 (s,
6H), 3.04 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.98 (dd, Jgem = 17.9 Hz, J = 2.4
Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 165.0, 159.0, 155.6,
153.2, 152,7, 151.8, 143.2, 139.7, 137.0, 136.9, 136.5, 133.1, 128.7, 128.6,
128.5x2, 128.2, 128.1, 127.9, 127.5x2, 127.4, 124.9, 109.2, 107.4, 107.0,
100.6, 94.3, 92.8, 77.8, 71.3, 71.1, 70.2, 68.4, 60.9x2, 56.3, 55.5, 26.0; HRMS
(ESI-TOF) calcd for C54H54NO11 [M+NH4]+
892.3697, found 892.3698.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-24)
Yield 48%; TLC Rf 0.59 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.26-7.45 (m, 20H,
aromatic), 7.17 (s, 2H), 6.78 (s, 2H), 6.28 (d, J = 1.9 Hz, 1H), 6.21 (d, J =
1.9 Hz, 1H), 5.60 (br s, 1H), 4.87-5.04 (m, 9H), 3.83 (s, 3H), 3.78 (s, 3H),
3.75 (s, 6H), 3.05 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.01 (dd, Jgem = 17.9
Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 165.2,
158.8, 155.3, 153.2, 152,5, 141.4, 139.6, 137.3, 136.9, 136.8, 133.2, 128.6,
128.4, 128.3, 128.2, 128.0, 127.8, 127.5, 127.4, 127.3, 125.2, 107.2, 106.9,
100.4, 94.1, 92.6, 77.5, 74.9, 71.3, 70.1, 68.6, 60.9, 56.2, 55.4, 25.7; HRMS
(ESI-TOF) calcd for C54H54NO11 [M+NH4]+
892.3697, found 892.3697.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-25)
Yield 41%; TLC Rf 0.57 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.42 (m, 27H,
aromatic), 6.61 (s, 2H), 6.39 (d, J = 1.9 Hz, 1H), 6.25 (d, J = 1.9 Hz, 1H),
5.66 (br s, 1H), 5.02-5.07 (m, 9H), 4.93 (s, 2H, Bn), 3.80 (s, 3H), 3.50 (s,
6H), 3.07 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.02 (dd, Jgem = 17.9 Hz, J =
2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 164.6, 158.7x2,
155.3, 153.2, 152,1, 142.2, 137.5, 137.1, 136.6, 136.2, 133.1, 128.8, 128.3x2,
128.2, 128.0, 127.9, 127.8, 127.6, 127.3, 125.1, 124.7, 108.9, 103.8, 100.3,
94.0, 92.5, 77.8, 74.8, 74.7, 70.8, 69.9, 68.1, 55.7, 55.2, 25.9; FT-IR (neat)
3031, 2938, 1716, 1621, 1593, 1499, 1455, 1429, 1369, 1328, 1214, 1148, 1124,
1030, 1002, 911, 815, 752, 697, 481 cm-1; HRMS (ESI-TOF) calcd for C60H58NO11
[M+NH4]+ 968.4010, found 968.4010.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-26)
Yield 43%; TLC Rf 0.51 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.27-7.42 (m, 22H,
aromatic), 6.60 (s, 2H), 6.40 (d, J = 1.9 Hz, 1H), 6.26 (d, J = 1.9 Hz, 1H),
5.66 (br s, 1H), 5.02-5.06 (m, 7H), 4.92 (s, 2H), 3.88 (s, 3H), 3.80 (s, 3H),
3.50 (s, 6H), 3.06 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.01 (dd, Jgem = 17.9
Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 164.7,
159.0, 158.9, 155.5, 153.4, 151,9, 143.7, 137.7, 136.8, 136.4, 133.3, 128.6,
128.4, 128.1, 128.0, 127.7x2, 127.5, 124.7, 109.2, 103.9, 100.5, 94.2, 92.7,
78.0, 74.9, 71.0, 70.1, 68.3, 61.0, 55.8, 55.4, 26.1; FT-IR (neat) 3031, 2938,
1716, 1620, 1593, 1499, 1455, 1428, 1370, 1329, 1216, 1148, 1124, 1030, 1002,
910, 842, 814, 753, 698, 477 cm-1; HRMS (ESI-TOF) calcd for C54H54NO11
[M+NH4]+ 892.3697, found 892.3697.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-27)
Yield 40%; TLC Rf 0.38 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.24-7.43 (m, 16H),
7.16 (d, J = 1.4 Hz, 1H), 6.63 (s, 2H), 6.37 (d, J = 2.4 Hz, 1H), 6.24 (d, J =
2.4 Hz, 1H), 5.66 (br s, 1H), 5.02-5.09 (m, 5H), 4.93 (s, 2H, Bn), 3.87 (s,
3H), 3.80 (s, 3H), 3.79 (s, 3H), 3.57 (s, 6H), 3.07 (dd, Jgem = 17.4 Hz, J =
4.3 Hz, 1H), 3.02 (dd, Jgem = 17.4 Hz, J = 2.4 Hz, 1H); 13C NMR
(67.8 MHz, CDCl3) δ 164.9, 158.9x2, 155.5, 153.4, 153,0, 151.7,
143.0, 137.7, 136.8, 136.4, 133.4, 128.6x2, 128.4, 128.1x2, 128.0, 127.8,
127.5, 124.9, 109.0, 107.3, 103.9, 100.4, 94.2, 92.7, 77.9, 74.9, 71.0, 70.1,
68.4, 60.9, 56.2, 55.9, 55.4, 26.0; FT-IR (neat) 2936, 1715, 1620, 1592, 1500,
1454, 1421, 1358, 1330, 1218, 1147, 1122, 1029, 1001, 814, 753, 698 cm-1;
HRMS (ESI-TOF) calcd for C48H50NO11 [M+NH4]+
816.3384, found 816.3380.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-28)
Yield 44%; TL C Rf 0.39 (toluene/ethyl
acetate = 10/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.43 (m,
15H, aromatic), 7.16 (s, 2H), 6.67 (s, 2H), 6.33 (d, J = 2.4 Hz, 1H), 6.21 (d, J
= 2.4 Hz, 1H), 5.65 (br s, 1H), 5.08 (s, 1H), 5.05 (s, 4H, Bn), 4.95 (s, 2H,
Bn), 3.78 (s, 3H), 3.77 (s, 6H), 3.65 (s, 6H), 3.08 (dd, Jgem = 17.9 Hz, J =
4.3 Hz, 1H), 3.02 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); HRMS (ESI-TOF) calcd
for C48H50NO11 [M+NH4]+ 816.3384,
found 816.3384.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-29)
Yield 47%; TLC Rf 0.40 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.41 (m, 22H,
aromatic), 6.61 (s, 2H), 6.39 (d, J = 2.4 Hz, 1H), 6.26 (d, J = 2.4 Hz, 1H),
5.66 (br s, 1H), 4.99-5.07 (m, 9H), 3.80 (s, 3H), 3.78 (s, 3H), 3.53 (s, 6H),
3.06 (dd, Jgem = 17.9 Hz, J = 4.4 Hz, 1H), 3.01 (dd, Jgem = 17.9 Hz, J = 1.9
Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 164.8, 158.9x2,
155.5, 153.1, 152,2, 142.3, 137.8, 137.2, 136.7, 136.4, 133.2, 128.5x2, 128.2,
128.1, 128.0, 127.7, 127.5, 124.9, 109.0, 103.9, 100.4, 94.2, 92.7, 78.0, 75.0,
71.0, 70.1, 68.3, 60.7, 55.8, 55.4, 26.1; FT-IR (neat) 3031, 2937, 1716, 1620,
1592, 1499, 1455, 1429, 1367, 1328, 1214, 1148, 1123, 1029, 1006, 910, 814,
753, 697 cm-1; HRMS (ESI-TOF) calcd for C54H54NO11
[M+NH4]+ 892.3697, found 892.3724.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-30)
Yield 46%; TLC Rf 0.34 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.28-7.41 (m, 15H,
aromatic), 7.25 (s, 2H), 6.60 (s, 2H), 6.40 (d, J = 2.4 Hz, 1H), 6.26 (d, J =
2.4 Hz, 1H), 5.66 (br s, 1H), 5.01-5.09 (m, 7H), 3.88 (s, 3H), 3.80 (s, 3H),
3.78 (s, 3H), 3.53 (s, 6H), 3.06 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.00
(dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 164.7, 159.0, 158.9, 155.5, 153.1, 151,9, 143.7, 137.8, 136.7, 136.4, 133.2,
128.6, 128.1, 128.0, 127.7, 127.5, 124.7, 109.1, 103.9, 100.5, 94.2, 92.7,
78.0, 70.9, 70.1, 68.2, 61.0, 60.7, 55.8, 55.4, 26.1; FT-IR (neat) 2939, 1716,
1620, 1592, 1499, 1455, 1428, 1369, 1329, 1216, 1148, 1123, 1037, 1004, 814,
754, 698 cm-1; HRMS (ESI-TOF) calcd for C48H50NO11
[M+NH4]+ 816.3384, found 816.3384.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-31)
Yield 49%; TLC Rf 0.27 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.26-7.43 (m, 11H,
aromatic), 7.15 (d, J = 1.9 Hz, 1H), 6.64 (s, 2H), 6.37 (d, J = 1.9 Hz, 1H,),
6.24 (d, J = 1.9 Hz, 1H), 5.67 (br s, 1H), 5.02-5.09 (m, 5H), 3.87 (s, 3H),
3.80 (s, 3H), 3.79x2 (s, 3H), 3.60 (s, 6H), 3.07 (dd, Jgem = 17.4 Hz, J = 4.4
Hz, 1H), 3.01 (dd, Jgem = 17.9 Hz, J = 1.9 Hz, 1H); 13C NMR (67.8
MHz, CDCl3) δ 165.0, 159.0, 158.9, 155.5, 153.2, 151,7, 143.1,
137.9, 136.8, 136.5, 133.3, 128.7x2, 128.2, 128.1, 127.9, 127.6, 124.9, 109.0,
107.3, 103.9, 100.5, 94.2, 92.8, 78.0, 71.0, 70.2, 68.5, 61.0, 60.8, 56.3,
55.9, 55.5, 26.2; FT-IR (neat) 2939, 1716, 1620, 1593, 1500, 1455, 1421, 1358,
1331, 1219, 1148, 1123, 1037, 1005, 814, 756, 698 cm-1; HRMS
(ESI-TOF) calcd for C42H46NO11 [M+NH4]+
740.3071, found 740.3073.
(2R*,3R*)-7-Benzyloxy-5-methoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-32)
Yield 43%; TLC Rf 0.28 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.43 (m, 10H,
aromatic), 7.16 (s, 2H), 6.68 (s, 2H, b), 6.32 (d, J = 1.9 Hz, 1H), 6.21 (d, J =
1.9 Hz, 1H), 5.65 (br s, 1H), 5.07 (s, 1H), 5.05 (s, 4H, Bn), 3.80 (s, 3H),
3.78 (s, 3H), 3.77 (s, 6H), 3.69 (s, 6H j), 3.05 (br s, 1H), 3.04 (br s, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 165.1, 158.8x2, 155.4, 153.1x2, 141.1,
137.8, 137.2, 136.8, 133.3, 128.6, 128.4, 128.2, 128.0x2, 127.5 125.1, 107.1,
103.8, 100.4, 94.1, 92.6, 77.8, 74.9, 70.1, 68.6, 60.8, 56.2, 55.9, 55.4, 25.9;
HRMS (ESI-TOF) calcd for C42H46NO11 [M+NH4]+
740.3071, found 740.3101.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-33)
Yield 39%; TLC Rf 0.66 (toluene/ethyl acetate
= 9/1); 1H NMR (400 MHz, CDCl3) δ 7.19-7.43 (m, 37H,
aromatic), 6.74 (s, 2H), 6.32 (d, J = 2.4 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H),
5.67 (br s, 1H), 4.91-5.06 (m, 11H), 4.81 (d, Jgem = 11.6 Hz, 2H), 4.68 (d, Jgem
= 11.6 Hz, 2H), 3.78 (s, 3H, f), 3.12 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H),
3.06 (dd, Jgem = 17.9 Hz, J = 1.9 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 164.8, 159.7, 158.0, 155.6, 152,8, 152.4, 142.7, 138.4, 137.7, 137.4, 136.9,
136.8, 136.4, 133.2, 128.5x3, 128.3x2, 128.2, 128.1, 128.0, 127.9, 127.8x2,
127.7, 127.6, 127,5, 127.2, 125.0, 109.1, 106.7, 100.7, 93.6, 93.3, 77.9, 75.1,
75.0, 71.2, 71.0, 70.0, 68.3, 55.4, 26.1; FT-IR (neat) 3031, 2935, 1717, 1620,
1592, 1499, 1454, 1429, 1370, 1328, 1196, 1148, 1112, 1029, 909, 814, 736, 696,
476 cm-1; HRMS (ESITOF) calcd for C72H66NO11
[M+NH4]+ 1120.4636, found 1120.4625.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-34)
Yield 41%; TLC Rf 0.61 (toluene/ethyl acetate
= 9/1); 1H NMR (400 MHz, CDCl3) δ 7.19-7.42 (m, 32H,
aromatic), 6.72 (s, 2H), 6.33 (d, J = 1.9 Hz, 1H), 6.25 (d, J = 1.9 Hz, 1H),
5.66 (br s, 1H), 4.90-5.06 (m, 9H), 4.76 (d, Jgem = 11.6 Hz, 2H), 4.63 (d, Jgem
= 11.6 Hz, 2H), 3.78 (s, 6H), 3.12 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.05
(dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 164.7, 159.7, 158.0, 155.7, 152,8, 152.0, 142.0, 137.7, 136.9, 136.8, 136.4,
133.2, 128.6, 128.5, 128.3, 128.0, 127.9, 127.7x2, 127.5, 127.4, 127.2, 124.7,
109.2, 106.7, 100.7, 93.6, 93.3, 77.9, 75.1, 71.1, 71.0, 70.0, 68.2, 60.8,
55.4, 26.2; FT-IR (neat) 3032, 2925, 1716, 1621, 1592, 1499, 1454, 1371, 1329,
1217, 1197, 1148, 1113, 1029, 1003, 909, 814, 737, 697, 477 cm-1;
HRMS (ESI-TOF) calcd for C66H62NO11 [M+NH4]+
1044.4323, found 1044.4319.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-35)
Yield 43%; TLC Rf 0.49 (toluene/ethyl acetate
= 9/1); 1H NMR (400 MHz, CDCl3) δ 7.21-7.43 (m, 27H,
aromatic), 6.75 (s, 2H), 6.29 (d, J = 1.9 Hz, 1H), 6.23 (d, J = 1.9 Hz, 1H),
5.66 (br s, 1H), 4.96-5.15 (m, 7H), 4.85 (d, Jgem = 11.6 Hz, 2H), 4.71 (d, Jgem
= 11.6 Hz, 2H), 3.78 (s, 3H, f), 3.77 (s, 3H), 3.75 (s, 3H), 3.12 (dd, Jgem =
17.9 Hz, J = 4.3 Hz, 1H), 3.05 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); HRMS
(ESI-TOF) calcd for C60H58NO11 [M+NH4]+
968.4010, found 968.4011.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-36)
Yield 40%; TLC Rf 0.53 (toluene/ethyl acetate
= 9/1); 1H NMR (400 MHz, CDCl3) δ 7.19-7.44 (m, 27H,
aromatic), 6.80 (s, 2H), 6.24 (d, J = 2.4 Hz, 1H), 6.20 (d, J = 2.4 Hz, 1H),
5.64 (br s, 1H), 4.93-5.07 (m, 9H), 4.85 (d, Jgem = 11.6 Hz, 2H, Bn), 3.78 (s,
3H), 3.76 (s, 6H), 3.12 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.05 (dd, Jgem =
17.9 Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ
165.2, 159.7, 157.9, 155.5, 153.2, 153,0, 152.8, 137.7, 137.4, 136.9, 136.8,
133.4, 128.5x2, 128.4, 128.2x2, 128.1, 127.9, 127.8, 127.7, 127.5x2, 127.4,
127.2, 125.2, 107.2, 106.8, 100.6, 93.6, 93.2, 77.6, 75.1, 74.9, 71.4, 69.9,
68.6, 56.3, 55.4, 25.9; FT-IR (neat) 3032, 2937, 1716, 1621, 1593, 1500, 1455,
1436, 1416, 1360, 1333, 1218, 1198, 1148, 1126, 1029, 911, 815, 751, 735, 697,
476 cm-1; HRMS (ESI-TOF) calcd for C60H58NO11
[M+NH4]+ 968.4010, found 968.4017.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-37)
Yield 47%; TLC Rf 0.51 (toluene/ethyl acetate
= 9/1); 1H NMR (400 MHz, CDCl3) δ 7.22-7.42 (m, 32H,
aromatic), 6.71 (s, 2H), 6.29 (d, J = 2.4 Hz, 1H), 6.24 (d, J = 2.4 Hz, 1H),
5.64 (br s, 1H), 5.01-5.05 (m, 7H), 4.92 (s, 2H, Bn), 4.83 (d, Jgem = 11.6 Hz,
2H, Bn), 4.72 (d, Jgem = 11.6 Hz, 2H, Bn), 3.81 (s, 3H), 3.77 (s, 3H), 3.11
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.04 (dd, Jgem = 17.9 Hz, J = 1.9 Hz,
1H); 13C NMR (67.8 MHz, CDCl3) δ 164.8, 159.7, 158.0,
155.6, 152.6, 152.3, 142.7, 139.5, 137.4, 136.9, 136.8, 136.4, 133.0, 130.0,
128.5, 128.4x2, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.4, 127.3, 127.2,
124.9, 115.0, 109.2, 106.8, 100.6, 93.6, 93.2, 77.8, 75.0, 71.1, 71.0, 70.0,
68.2, 60.8, 55.4, 26.1; FT-IR (neat) 3032, 2936, 1716, 1621, 1592, 1500, 1455,
1435, 1367, 1332, 1218, 1197, 1148, 1115, 1029, 814, 736, 697, 474 cm-1;
HRMS (ESI-TOF) calcd for C66H62NO11 [M+NH4]+
1044.4323, found 1043.4330.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-38)
Yield 58%; TLC Rf 0.43 (toluene/ethyl acetate
= 9/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.44 (m, 27H,
aromatic), 6.69 (s, 2H, a), 6.30 (d, J = 1.9 Hz, 1H), 6.25 (d, J = 1.9 Hz, 1H),
5.64 (br s, 1H), 5.03-5.05 (m, 6H, Bn), 4.99 (s, 1H), 4.79 (d, J = 11.6 Hz, 2H,
Bn), 4.67 (d, J = 11.6 Hz, 2H, Bn), 3.80 (s, 3H), 3.78 (s, 3H), 3.77 (s, 3H),
3.10 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.03 (dd, Jgem = 17.9 Hz, J = 1.9
Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 164.7, 159.7, 158.0,
155.7, 152.6, 143.7, 139.5, 136.9, 136.8, 136.4, 133.0, 128.6, 128.5, 128.4,
128.0, 127.9, 127.7x2, 127.4, 127.3, 127.2, 124.7, 109.2, 106.8, 100.7, 93.6,
93.3, 77.9, 71.1, 71.0, 70.0, 68.2, 60.8, 55.4, 26.2; HRMS (ESI-TOF) calcd for
C60H58NO11 [M+NH4]+ 968.4010, found
968.4034.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-39)
Yield 54%; TLC Rf 0.29 (toluene/ethyl acetate
= 9/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.41 (m, 22H,
aromatic), 6.73 (s, 2H), 6.27 (d, J = 1.9 Hz, 1H), 6.23 (d, J = 1.9 Hz, 1H),
5.64 (br s, 1H), 5.03-5.05 (m, 4H, Bn), 5.00 (s, 1H), 4.87 (d, Jgem = 11.6 Hz,
2H, Bn), 4.75 (d, Jgem = 11.6 Hz, 2H, Bn), 3.81 (s, 3H), 3.78 (s, 3H,), 3.78
(s, 6H), 3.11 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.04 (dd, Jgem = 17.9 Hz, J
= 1.9 Hz, 1H); FT-IR (neat) 2925, 1716, 1620, 1592, 1500, 1434, 1373, 1331,
1219, 1147, 1115, 1029, 1006, 814, 772, 697 cm-1; HRMS (ESI-TOF) calcd for C54H54NO11
[M+NH4]+ 892.3697, found 892.3684.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
4- benzyloxy-3,5-dimethoxybenzoate (Protected-40)
Yield 51%; TLC Rf 0.34 (toluene/ethyl acetate
= 9/1); 1H NMR (400 MHz, CDCl3) δ 7.29-7.44 (m, 20H,
aromatic), 7.18 (s, 2H), 6.78 (s, 2H), 6.22 (d, J = 1.9 Hz, 1H), 6.20 (d, J =
1.9 Hz, 1H), 5.62 (br s, 1H), 5.05 (s, 1H), 5.03 (s, 2H, Bn), 4.99 (d, Jgem =
11.6 Hz, 2H, Bn), 4.94 (s, 2H, Bn), 4.89 (d, J = 11.6 Hz, 2H, Bn), 3.83 (s,
3H), 3.78 (s, 3H), 3.76 (s, 6H), 3.12 (dd, Jgem = 18.4 Hz, J = 4.3 Hz, 1H),
3.05 (dd, Jgem = 18.4 Hz, J = 2.9 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 165.2, 159.7, 157.9, 155.5, 153.2, 152.6, 141.5, 139.6, 137.3, 136.9, 136.8,
133.1, 128.5, 128.4, 128.2x2, 127.9x2, 127.8, 127.3, 127.1, 125.2, 107.2,
106.9, 100.6, 93.5, 93.1, 77.5, 74.9, 71.3, 69.9, 68.6, 60.9, 56.2, 55.4, 25.8;
HRMS (ESI-TOF) calcd for C54H54NO11 [M+NH4]+
892.3697, found 892.3695.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-41)
Yield 43%; TLC Rf 0.49 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.27-7.43 (m, 27H,
aromatic), 6.61 (s, 2H), 6.34 (d, J = 2.4 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H),
5.67 (br s, 1H), 5.02-5.07 (m, 9H), 4.92 (s, 2H, Bn), 3.78 (s, 3H), 3.51 (s,
6H), 3.13 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.07 (dd, Jgem = 17.9 Hz, J =
1.9 Hz, 1H); HRMS (ESI-TOF) calcd for C60H58NO11
[M+NH4]+ 968.4010, found 968.4044.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-42)
Yield 38%; TLC Rf 0.44 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.27-7.42 (m, 22H,
aromatic), 6.60 (s, 2H), 6.34 (d, J = 2.4 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H),
5.67 (br s, 1H), 5.02-5.09 (m, 7H), 4.92 (s, 2H, Bn), 3.88 (s, 3H), 3.78 (s,
3H), 3.50 (s, 6H), 3.13 (dd, Jgem = 17.9 Hz, J = 3.9 Hz, 1H), 3.07 (dd, Jgem =
17.9 Hz, J = 1.9 Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ
164.8, 159.7, 158.0, 155.7, 153.4 152.0, 137.7, 136.8, 136.5, 133.3, 128.6,
128.5, 128.4, 128.1, 127.9, 127.7x2, 127.2, 124.8, 109.3, 104.0, 100.7, 93.6,
93.3, 78.0, 74.9, 71.0, 70.0, 68.3, 61.0, 55.9, 55.4, 26.3; HRMS (ESI-TOF)
calcd for C54H54NO11 [M+NH4]+
892.3697, found 892.3690.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-43)
Yield 39%; TLC Rf 0.31 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.27-7.43 (m, 16H, a
and aromatic), 7.16 (d, J = 1.9 Hz, 1H), 6.64 (s, 2H), 6.32 (d, J = 1.9 Hz,
1H), 6.23 (d, J = 1.9 Hz, 1H), 5.68 (br s, 1H), 5.09 (s, 1H), 5.05 (s, 4H, Bn),
4.93 (s, 2H, Bn), 3.88 (s, 3H), 3.81 (s, 3H), 3.78 (s, 3H), 3.58 (s, 6H), 3.14
(dd, Jgem = 17.9 Hz, J = 4.4 Hz, 1H), 3.08 (dd, Jgem = 17.9 Hz, J = 2.4 Hz,
1H); 13C NMR (67.8 MHz, CDCl3) δ 164.9, 159.7, 158.0,
155.7, 153.4, 153.1, 151.7, 143.1, 137.7, 136.8, 136.5, 133.3, 128.6, 128.5,
128.4, 128.1x2, 127.9, 127.7, 127.2, 124.9, 109.1, 107.3, 104.0, 100.6, 93.6,
93.3, 77.9, 74.9, 71.0, 70.0, 68.4, 60.9, 56.2, 55.9, 55.4, 26.2; HRMS
(ESI-TOF) calcd for C48H50NO11 [M+NH4]+
816.3384, found 816.3392.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-(3-hydroxy-4,5-dimethoxyphenyl)chroman-3-yl
4-hydroxy-3,5-dimethoxybenzoate (Protected-44)
Yield 39%; TLC Rf 0.33 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.17-7.35 (m, 15H,
aromatic), 7.09 (s, 2H), 6.61 (s, 2), 6.20 (d, J = 2.4 Hz, 1H), 6.13 (d, J =
2.4 Hz, 1H), 5.60 (br s, 1H), 5.02 (s, 1H), 4.97 (s, 2H, Bn), 4.96 (s, 2H, Bn),
4.87 (s, 2H, Bn), 3.85 (s, 6H), 3.76 (s, 3H), 3.73 (s, 3H), 3.04 (dd, Jgem =
16.9 Hz, J = 4.3 Hz, 1H), 2.84 (dd, Jgem = 17.4 Hz, J = 2.4 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 165.3, 159.7, 157.9, 155.6, 153.4, 153.2,
141.3, 137.7, 137.2, 136.8, 133.4, 128.5, 128.4, 128.2, 128.1, 129.0, 127.9,
127.7, 127.2, 125.2, 107.2, 104.0, 100.6, 93.6, 93.2, 77.9, 74.9, 70.0, 68.6,
56.2, 56.0, 55.3, 25.7; HRMS (ESI-TOF) calcd for C48H50NO11
[M+H]+ 816.3384, found 816.3383.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-45)
Yield 52%; TLC Rf 0.32 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.42 (m, 22H,
aromatic), 6.61 (s, 2H), 6.33 (d, J = 2.4 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H),
5.68 (br s, 1H), 5.02-5.08 (m, 9H), 3.78 (s, 3H), 3.78 (s, 3H), 3.53 (s, 6H),
3.13 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.07 (dd, Jgem = 17.9 Hz, J = 1.9
Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 164.8, 159.7, 158.0,
155.7, 153.1, 152.3, 142.4, 137.9, 137.3, 136.8, 136.5, 133.2, 128.5x2, 128.2,
128.1, 128.0x2, 127.9, 127.7, 127.2, 124.9, 109.1, 104.0, 100.7, 93.6, 93.3,
78.1, 75.0, 71.0, 70.0, 68.3, 60.7, 55.8, 55.4, 26.3; HRMS (ESI-TOF) calcd for
C54H54NO11 [M+NH4]+ 892.3697, found
892.3719.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-46)
Yield 54%; TLC Rf 0.28 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.28-7.42 (m, 17H,
aromatic), 6.60 (s, 2H), 6.34 (d, J = 2.4 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H),
5.68 (br s, 1H), 5.02-5.09 (m, 7H), 3.88 (s, 3H), 3.78 (s, 6H), 3.53 (s, 6H),
3.13 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.06 (dd, Jgem = 17.9 Hz, J = 1.9
Hz, 1H); 13C NMR (67.8 MHz, CDCl3) d 164.8, 159.7, 158.0,
155.7, 153.1, 152.0, 143.8, 137.9, 136.8, 136.5, 133.1, 128.6, 128.5, 128.1,
127.9, 127.6, 127.2, 124.7, 109.3, 104.0, 100.6, 93.6, 93.3, 78.0, 71.0, 70.0,
68.2, 60.9, 60.7, 55.8, 55.4, 26.3; HRMS (ESI-TOF) calcd for C48H50NO11
[M+NH4]+ 816.3384, found 816.3375.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-47)
Yield 58%; TLC Rf 0.15 (toluene/ethyl acetate
= 10/1); 1H NMR (400 MHz, CDCl3) δ 7.27-7.42 (m, 11H),
7.16 (d, J = 1.9 Hz, 1H), 6.64 (s, 2H), 6.31 (d, J = 1.9 Hz, 1H), 6.24 (d, J =
1.9 Hz, 1H), 5.68 (br s, 1H), 5.08 (s, 1H), 5.06 (s, 2H, Bn), 5.05 (s, 2H, Bn),
3.87 (s, 3H), 3.81 (s, 3H), 3.79 (s, 3H), 3.78 (s, 3H), 3.61 (s, 6H), 3.14 (dd,
Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.08 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 164.9, 159.7, 158.0, 155.7, 153.1, 151.7,
143.1, 137.9, 136.8, 136.5, 133.2, 128.6, 128.5, 128.1, 127.9, 127.7, 127.5,
127.1, 124.8, 109.1, 107.3, 103.9, 100.6, 93.6, 93.2, 77.9, 71.0, 70.0, 68.4,
60.9, 60.7, 56.2, 55.9, 55.4, 26.2; FT-IR (neat) 2927, 1716, 1621, 1593, 1502,
1456, 1422, 1357, 1331, 1221, 1149, 1124, 1004, 814, 756, 699 cm-1;
HRMS (ESI-TOF) calcd for C42H46NO11 [M+NH4]+
740.3071, found 740.3099.
(2R*,3R*)-5-Benzyloxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
4- benzyloxy-3,5-dimethoxybenzoate (Protected-48)
Yield 53%; TLC Rf 0.19 (toluene/ethyl acetate
= 9/1); 1H NMR (400 MHz, CDCl3) δ 7.28-7.44 (m, 10H,
aromatic), 7.16 (s, 2H), 6.69 (s, 2H), 6.26 (d, J = 2.4 Hz, 1H), 6.21 (d, J =
2.4 Hz, 1H), 5.67 (br s, 1H), 5.09 (s, 1H), 5.05 (s, 2H, Bn), 5.04 (s, 2H, Bn),
3.80 (s, 3H), 3.79 (s, 3H), 3.78 (s, 6H), 3.69 (s, 6H), 3.14 (dd, Jgem = 17.9
Hz, J = 4.3 Hz, 1H), 3.09 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3) δ 165.1, 159.6, 157.9, 155.6, 153.2, 153.1,
141.2, 137.9, 137.2, 136.8, 133.3, 128.5, 128.4, 128.2, 128.0, 127.9, 127.1,
125.2, 107.2, 103.9, 100.6, 93.6, 93.2, 77.9, 74.9, 69.9, 68.6, 60.8, 56.2,
56.0, 55.4, 26.1; HRMS (ESI-TOF) calcd for C42H46NO11
[M+NH4]+ 740.3071, found 740.3074.
(2R*,3R*)-5,7-Dimethoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-49)
Yield 45%; TLC Rf 0.60 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.19-7.36 (m, 32H,
aromatic), 6.74 (s, 2H), 6.30 (d, J = 2.4 Hz, 1H), 6.17 (d, J = 2.4 Hz, 1H),
5.66 (br s, 1H), 4.90-5.04 (m, 9H), 4.81 (d, Jgem = 11.6 Hz, 2H, Bn), 4.68 (d, Jgem
= 11.6 Hz, 2H, Bn), 3.81 (s, 3H), 3.79 (s, 3H, f or g), 3.06 (dd, Jgem = 17.9
Hz, J = 4.3 Hz, 1H, h), 3.00 (dd, Jgem = 17.9 Hz, J = 1.9 Hz, 1H, h).
(2R*,3R*)-5,7-Dimethoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-50)
Yield 51%; TLC Rf 0.58 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.19-7.38 (m, 27H,
aromatic), 6.72 (s, 2H), 6.30 (d, J = 1.9 Hz, 1H), 6.17 (d, J = 1.9 Hz, 1H),
5.65 (br s, 1H), 4.95-5.06 (m, 7H), 4.77 (d, Jgem = 11.6 Hz, 2H, Bn), 4.64 (d, Jgem
= 11.6 Hz, 2H, Bn), 3.81 (s, 3H), 3.79 (s, 3H), 3.77 (s, 3H), 3.05 (dd, Jgem =
17.9 Hz, J = 3.9 Hz, 1H), 2.98 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H).
(2R*,3R*)-5,7-Dimethoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-51)
Yield 38%; TLC Rf 0.53 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.14-7.38 (m, 22H,
aromatic), 6.76 (s, 2H), 6.27 (d, J = 1.9 Hz, 1H), 6.15 (d, J = 1.9 Hz, 1H),
5.65 (br s, 1H), 4.96-5.07 (m, 5H), 4.85 (d, Jgem = 11.6 Hz, 2H, Bn), 4.72 (d, Jgem
= 11.6 Hz, 2H, Bn), 3.80 (s, 3H), 3.79 (s, 3H), 3.78 (s, 3H), 3.77 (s, 3H),
3.06 (dd, Jgem = 18.4 Hz, J = 4.3 Hz, 1H), 3.00 (dd, Jgem = 18.4 Hz, J = 2.4
Hz, 1H).
(2R*,3R*)-5,7-Dimethoxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-52)
Yield 29%; TLC Rf 0.54 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.18-7.45 (m, 22H,
aromatic), 6.81 (s, 2H), 6.22 (d, J = 1.9 Hz, 1H), 6.12 (d, J = 1.9 Hz, 1H),
5.63 (br s, 1H, d), 4.97-5.08 (m, 5H), 4.94 (d, Jgem = 11.6 Hz, 2H, Bn), 4.86
(d, Jgem = 11.6 Hz, 2H, Bn), 3.80 (s, 3H), 3.79 (s, 3H), 3.76 (s, 6H), 3.07
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.01 (dd, Jgem = 17.9 Hz, J = 2.4 Hz,
1H).
(2R*,3R*)-5,7-Dimethoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-53)
Yield 43%; TLC Rf 0.58 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.24-7.34 (m, 27H,
aromatic), 6.73 (s, 2H), 6.28 (d, J = 2.4 Hz, 1H), 6.17 (d, J = 2.4 Hz, 1H),
5.64 (br s, 1H), 5.05 (s, 1H), 5.02 (s, 4H, Bn), 4.92 (s, 2H, Bn), 4.84 (d, Jgem
= 11.6 Hz, 2H, Bn), 4.73 (d, Jgem = 11.6 Hz, 2H, Bn), 3.81 (s, 6H), 3.79 (s,
3H), 3.05 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.99 (dd, Jgem = 17.9 Hz, J =
2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 164.8, 159.7,
158.9, 155.5, 152.5, 152.3, 142.7, 139.4, 137.4, 136.9, 136.4, 133.0, 128.5,
128.4x2, 128.2, 128.1, 128.0, 127.8, 127.7, 127.3, 124.9, 109.1, 106.7, 100.1,
93.2, 91.9, 77.8, 75.0, 71.1, 71.0, 68.2, 60.8, 55.4, 55.3, 26.0.
(2R*,3R*)-5,7-Dimethoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-54)
Yield 47%; TLC Rf 0.56 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.22-7.40 (m, 22H,
aromatic), 6.70 (s, 2H), 6.28 (d, J = 2.4 Hz, 1H), 6.16 (d, J = 2.4 Hz, 1H),
5.63 (br s, 1H), 5.06 (s, 1H), 5.03x2 (s, 4H, Bn), 4.79 (d, Jgem = 12.1 Hz, 2H,
Bn), 4.67 (d, Jgem = 12.1 Hz, 2H, Bn), 3.81 (s, 3H), 3.80 (s, 3H), 3.78x2 (s,
3H), 3.03 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.97 (dd, Jgem = 17.9 Hz, J =
2.4 Hz, 1H).
(2R*,3R*)-5,7-Dimethoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-55)
Yield 40%; TLC Rf 0.51 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.27-7.38 (m, 16H, a
and aromatic), 7.17 (d, J = 1.9 Hz, 1H), 6.73 (s, 2H), 6.25 (d, J = 2.4 Hz,
1H), 6.14 (d, J = 2.4 Hz, 1H), 5.63 (br s, 1H), 5.01-5.04 (m, 3H), 4.87 (d, Jgem
= 11.6 Hz, 2H, Bn), 4.76 (d, Jgem = 11.6 Hz, 2H, Bn), 3.81 (s, 3H), 3.80 (s,
3H), 3.79 (s, 3H), 3.78 (s, 6H), 3.04 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H),
2.98 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 165.0, 159.9, 159.0, 155.6, 153.2, 152.7, 151.9, 137.1, 136.6, 133.2, 128.7,
128.6, 128.5, 128.2, 127.9, 127.5, 127.4, 125.0, 109.2, 107.5, 100.3, 93.4,
92.0, 77.9, 71.4, 71.1, 68.5, 61.0, 60.9, 56.4, 55.5x2, 26.0.
(2R*,3R*)-5,7-Dimethoxy-2-[3,5-bis(benzyloxy)-4-methoxyphenyl]chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-56)
Yield 32%; TLC Rf 0.52 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.28-7.42 (m, 15H,
aromatic), 7.17 (s, 2H), 6.78 (s, 2H), 6.20 (d, J = 2.4 Hz, 1H), 6.11 (d, J =
2.4 Hz, 1H), 5.61 (br s, 1H), 5.04 (s, 1H), 5.00 (d, Jgem = 11.6 Hz, 2H, Bn),
4.93 (s, 2H, Bn), 4.89 (d, Jgem = 11.6 Hz, 2H, Bn), 3.83 (s, 3H), 3.79 (s, 3H),
3.78 (s, 3H, g, h or i), 3.76 (s, 6H, j), 3.05 (dd, Jgem = 17.9 Hz, J = 4.3 Hz,
1H), 3.03 (br s, 1H).
(2R*,3R*)-5,7-Dimethoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-57)
Yield 34%; TLC Rf 0.55 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.24-7.34 (m, 27H,
aromatic), 6.73 (s, 2H), 6.28 (d, J = 2.4 Hz, 1H), 6.17 (d, J = 2.4 Hz, 1H),
5.64 (br s, 1H), 5.05 (s, 1H), 5.02 (s, 2H, Bn), 4.92 (s, 2H, Bn), 4.84 (d, J =
11.6 Hz, 2H, Bn), 4.73 (d, J = 11.6 Hz, 2H, Bn), 3.81 (s, 6H), 3.79 (s, 3H),
3.75 (s, 6H), 3.05 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 2.99 (dd, Jgem = 17.9
Hz, J = 2.4 Hz, 1H).
(2R*,3R*)-5,7-Dimethoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-58)
Yield 39%; TLC Rf 0.52 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.24-7.42 (m, 17H,
aromatic), 6.61 (s, 2H), 6.32 (d, J = 2.4 Hz, 1H), 6.17 (d, J = 2.4 Hz, 1H),
5.66 (br s, 1H), 5.02-5.09 (m, 5H), 4.92 (s, 2H, Bn), 3.88 (s, 3H), 3.81 (s,
3H), 3.79 (s, 3H), 3.51 (s, 6H), 3.06 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H),
3.03 (br s, 1H).
(2R*,3R*)-5,7-Dimethoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-59)
Yield 52%; TLC Rf 0.47 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.24-7.43 (m, 11H, a
and aromatic), 7.16 (d, J = 1.9 Hz, 1H), 6.64 (s, 2H), 6.30 (d, J = 2.4 Hz,
1H), 6.15 (d, J = 2.4 Hz, 1H), 5.67 (br s, 1H), 5.08 (d, Jgem = 12.1 Hz, 1H,
Bn), 5.08 (s, 1H, f), 5.04 (d, Jgem = 12.1 Hz, 1H, Bn), 4.94 (s, 2H, Bn), 3.87
(s, 3H), 3.81 (s, 3H), 3.80 (s, 3H), 3.79 (s, 3H), 3.58 (s, 6H), 3.07 (dd, Jgem
= 17.4 Hz, J = 3.9 Hz, 1H), 3.04 (br s, 1H); 13C NMR (67.8 MHz, CDCl3)
δ 164.9, 159.7, 158.9, 155.4, 153.4, 151.7, 143.0, 137.7, 136.8, 133.4, 128.6,
128.4, 128.1x2, 127.7, 127.6, 124.9, 109.0, 107.3, 100.2, 93.2, 77.9, 74.9,
71.0, 68.5, 60.9, 56.2, 55.9, 55.4x2, 26.0.
(2R*,3R*)-5,7-Dimethoxy-2-(4-benzyloxy-3,5-dimethoxyphenyl)chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-60)
Yield 54%; TLC Rf 0.49 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 6.8 Hz,
2H, aromatic), 7.26-7.34 (m, 8H, aromatic), 7.16 (s, 2H), 6.68 (s, 2H), 6.25
(d, J = 1.9 Hz, 1H), 6.13 (d, J = 1.9 Hz, 1H), 5.65 (br s, 1H), 5.08 (s, 1H),
5.04 (s, 2H, Bn), 4.95 (s, 2H, Bn), 3.80 (s, 3H), 3.79 (s, 3H), 3.78 (s, 6H),
3.66 (s, 6H), 3.05 (br s, 2H).
(2R*,3R*)-5,7-Dimethoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3,4,5-tris(benzyloxy)benzoate (Protected-61)
Yield 48%; TLC Rf 0.53 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.25-7.38 (m, 17H,
aromatic), 6.62 (s, 2H), 6.32 (d, J = 1.9 Hz, 1H), 6.17 (d, J = 1.9 Hz, 1H),
5.67 (br s, 1H), 5.07-5.00 (m, 7H), 3.81 (s, 3H), 3.79 (s, 3H), 3.78 (s, 3H),
3.54 (s, 6H), 3.06 (dd, Jgem = 17.9 Hz, J = 3.9 Hz, 1H), 3.01 (d, Jgem = 17.9
Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 164.8, 159.7, 158.9,
155.5, 153.1, 152.2, 142.3, 137.8, 137.2, 136.4, 133.2, 128.5x2, 128.2, 128.1,
128.0, 127.7, 124.9, 109.0, 103.9, 100.1, 93.2, 91.9, 78.0, 75.0, 71.0, 68.3,
60.7, 55.8, 55.4x2, 26.1.
(2R*,3R*)-5,7-Dimethoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3,5-bis(benzyloxy)-4-methoxybenzoate (Protected-62)
Yield 51%; TLC Rf 0.50 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.29-7.40 (m, 12H,
aromatic), 6.61 (s, 2H), 6.32 (d, J = 1.9 Hz, 1H), 6.17 (d, J = 1.9 Hz, 1H),
5.67 (br s, 1H), 5.08 (d, Jgem = 11.6 Hz, 2H, Bn), 5.05 (s, 1H), 5.04 (d, Jgem
= 11.6 Hz, 2H, Bn), 3.88 (s, 3H), 3.81 (s, 3H), 3.79 (s, 3H), 3.78 (s, 3H),
3.54 (s, 6H), 3.06 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H), 3.00 (d, Jgem = 17.9
Hz, 1H); 13C NMR (67.8 MHz, CDCl3) δ 164.7, 159.7, 158.9,
155.5, 153.1, 151.9, 143.6, 137.8, 136.4, 133.2, 128.6, 128.1, 127.6, 124.7,
109.1, 103.8, 100.1, 93.2, 91.9, 78.0, 70.9, 68.2, 60.9, 60.7, 55.7, 55.4x2,
26.1.
(2R*,3R*)-5,7-Dimethoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
3-benzyloxy-4,5-dimethoxybenzoate (Protected-63)
Yield 47%; TLC Rf 0.46 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.29-7.40 (m, 5H,
aromatic), 7.27 (d, J = 1.9 Hz, 1H), 7.15 (d, J = 1.9 Hz, 1H), 6.64 (s, 2H),
6.29 (d, J = 2.4 Hz, 1H), 6.15 (d, J = 2.4 Hz, 1H), 5.67 (br s, 1H), 5.08 (d, Jgem
= 11.6 Hz, 1H, Bn), 5.07 (s, 1H, f), 5.04 (d, Jgem = 11.6 Hz, 1H, Bn), 3.87 (s,
3H), 3.81 (s, 3H), 3.80 (s, 3H), 3.79x2 (s, 3H), 3.61 (s, 6H), 3.07 (dd, Jgem =
17.9 Hz, J = 4.8 Hz, 1H), 3.02 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H); FT-IR
(neat) 3031, 2938, 1716, 1621, 1593, 1499, 1455, 1429, 1369, 1328, 1214, 1148,
1124, 1030, 1002, 911, 843, 815, 752, 697, 481 cm-1.
(2R*,3R*)-5,7-Dimethoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl
4-benzyloxy-3,5-dimethoxybenzoate (Protected-64)
Yield 36%; TLC Rf 0.48 (hexane/ethyl acetate
= 1/1); 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 6.8 Hz,
2H, aromatic), 7.28-7.34 (m, 3H, aromatic), 7.16 (s, 2H), 6.69 (s, 2H), 6.24
(d, J = 2.4 Hz, 1H), 6.12 (d, J = 2.4 Hz, 1H), 5.66 (br s, 1H), 5.08 (s, 1H),
5.04 (s, 2H, Bn), 3.80x2 (s, 3H), 3.79 (s, 3H), 3.78 (s, 6H), 3.70 (s, 6H),
3.05 (s, 1H), 3.04 (s, 1H); 13C NMR (67.8 MHz, CDCl3) δ
165.2, 159.8, 158.9, 155.6, 153.2x2, 141.3, 138.0, 137.3, 133.4, 128.4, 128.2,
128.0, 125.3, 107.3, 104.0, 100.2, 93.3, 91.9, 77.9, 75.0, 68.7, 60.8, 56.3x2,
56.0, 55.4, 26.0.
（２−２）収率
合成した６４種類のエピガロカテキンガレート誘導体の固相時及び脱保護時の収率を下表に示す。なお、表中の化合物の欄の番号は、図１中に記載されている化合物の番号と対応する。
Figure 2011162506
 〔実施例２〕 マウスメラノーマ細胞株 B16 に対するエピガロカテキンガレート誘導体の細胞増殖抑制作用
（１）実験方法
（１−１）細胞および細胞培養
マウスメラノーマ細胞株 B16 は 5% ウシ胎児血清 (FCS) (Paa
laboratories, Pasching, Austria) 添加 DMEM (Dulbecco’s modified Eagle’s medium)
(Cosmo Bio Co., LTD, Tokyo, Japan) で、37℃、水蒸気飽和した 5% CO2 条件下で継代、維持した。
DMEM 培地中には、100 U/mL ペニシリン（Meiji pharmaceutical
Company, Tokyo, Japan）、100 mg/mL ストレプトマイシン（Meiji pharmaceutical Company）、23.1
mM NaHCO3 (Wako, Tokyo, Japan)、そして 25 mM HEPES (Wako) を添加した。細胞は対数増殖期で培養維持した。
（１−２）エピガロカテキンガレート誘導体
エピガロカテキン-3-O-ガレート（epigallocatechin-3-O-gallate,
EGCG ）(Teavigo, DSM Nutritional Products, Grenzach-Wyhlen, Germany)及びその誘導体は、 5
mM となるように 10% DMSO-dH2O に溶解し、-20℃で凍結保存し、適宜希釈して用いた。なお、EGCG を Positive control として用いた。
（１−３）細胞増殖抑制作用の評価
B16 細胞を 1 x 104 cells/mL となるように
24 well plate に播種し、24 h 前培養を行い細胞を接着させた。その後、5 mg/mL BSA (Bovine serum albmin)
(Roche diagnostics, Mannheim, Germany)、200 U/mL catalase (Sigma, St. Louis, MO)、5
U/mL SOD (super oxide dismutase) (Sigma)、および終濃度 0、1、5 mM となるように各エピガロカテキンガレート誘導体を添加した
1% FCS-DMEM 培地に置換し、96 h 刺激をかけた。その後、細胞を回収し、細胞数をセルカウンター (Sysmex, Kobe, Japan) を用いて測定した。細胞増殖抑制活性はサンプルマイナス時の細胞数に対する相対値で表した。
（１−４）細胞生存率の評価
細胞生存率はトリパンブルー染色法で測定した。具体的には、1% Trypan blue 溶液（Trypan
Blue (Wako) を 1% となるように PBS に溶解）と細胞懸濁液が1 : 9 となるように混合し、血球計算盤で生存率を測定した。
（２）実験結果
実験に用いたエピガロカテキンガレート誘導体の構造式を図１に示す。また、各エピガロカテキンガレート誘導体の細胞生存率を図２に示す。
図に示すように、エピガロカテキンガレートのＡ環の７位がメトキシ基で、５位がヒドロキシ基である３３〜４８の化合物の細胞増殖抑制活性が高かった。
〔実施例３〕 A環7位を置換したエピガロカテキンガレートの合成
（１）６-ベンジルオキシ-４-[２-(２-クロロエトキシ)エトキシ]-２-ヒドロキシベンズアルデヒドの合成
エチレングリコールモノ-２-クロロメチルエチルエーテル (370 μL, 3.51
mmol)と塩化パラトルエンスルホン酸 (810 mg, 4.21 mmol)を塩化メチレン溶媒(18.0 mL)中トリエチルアミン(1.50 mL,
10.5 mmo)とトリメチルアミン塩酸塩hydrochloride (33.5 mg, 351 μmol, 0.100 eq.)存在下、氷冷下作用させた。そのまま３０分反応させた後、反応溶液を水と酢酸エチルの混合溶媒の中に注いだ。水相を酢酸エチル溶媒で抽出した。得られた有機相を飽和塩化アンモニウム水溶液、および飽和食塩水で洗浄し、硫酸マグネシウムで乾燥させた。溶媒を減圧下濃縮して得られた残査を次の反応に用いた。
残査をDMF(18.0 mL)に溶解させ、６-ベンジルオキシ-２、４-ジヒドロキシベンズアルデヒド(857
mg, 3.51 mmol)と炭酸カリウムK2CO3 (730 mg, 5.26 mmol)を加え、室温下１２時間反応させた。反応溶液を水と酢酸エチルの混合溶媒の中に注いだ。水相を酢酸エチル溶媒で抽出した。得られた有機相を飽和塩化アンモニウム水溶液、および飽和食塩水で洗浄し、硫酸マグネシウムで乾燥させた。溶媒を減圧下濃縮して得られた残査をシリカゲルカラムクロマトグラフィーで精製することにより（１０％酢酸エチル ヘキサン溶液）、目的とするベンゾアルデヒドを得た。(1.09
g, 3.10 mmol, 83% yield)
TLC Rf 0.43 (hexane/ethyl acetate = 2/1); 1H
NMR (400 MHz, CDCl3) δ12.5 (s, 1H, a), 10.2 (s, 1H, b), 7.36-7.41
(m, 5H, aromatic), 6.05 (d, J = 1.9 Hz, 1H, c or d), 6.02 (d, J = 8.1 Hz, 1H, c
or d), 5.08 (s, 2H, Bn), 4.15 (t, J = 4.8 Hz, 2H, e), 3.87 (t, J = 4.8 Hz, 2H,
f), 3.81 (t, J = 5.8 Hz, 2H, g), 3.65 (t, J = 5.8 Hz, 2H, h); 13C
NMR (100 MHz, CDCl3) δ192.0, 167.1, 166.3, 162.7, 135.8, 128.8,
128.4, 127.4, 106.4, 93.9, 92.3, 71.6, 70.6, 69.4, 67.8, 42.7; FT-IR (solid)
2922, 1779, 1635, 1500, 1436, 1377, 1297, 1214, 1175, 1113, 821, 740, 697, 541
cm-1.
Figure 2011162506
（２）６-ベンジルオキシ-３-ブロモ-４- [２-(２-クロロエトキシ)エトキシ] -２-ヒドロキシベンズアルデヒドの合成
６-ベンジルオキシ-４-[２-(２-クロロエトキシ)エトキシ]-２-ヒドロキシベンズアルデヒド(48.8
mg, 139 μmol) をCH2Cl2 (700 μL) に溶解し、臭素を (7.00 μL, 139 μmol)
氷冷下で加えた。そのままの温度で、一時間反応させた後、反応溶液を１０％チオ硫酸ナトリウム水溶液と飽和重炭酸水溶液と酢酸エチルの混合溶液の中に注いだ。水相を酢酸エチルで抽出し、得られた有機相を飽和食塩水で洗浄、硫酸マグネシウムで乾燥させた。減圧濃縮し、得られた残査をシリカゲルカラムクロマトグラフィーで精製（１５％酢酸エチル ヘキサン溶液）するこにより、目的とする臭素化体を白色固体として得た。
(58.4 mg, 136 μmol, 98% yield)
TLC Rf 0.37 (hexane/ethyl acetate = 2/1); 1H
NMR (400 MHz, CDCl3) δ13.0 (s, 1H, a), 10.2 (s, 1H, b), 7.39-7.41
(m, 5H, aromatic), 6.15 (s, 1H, c), 5.16 (s, 2H, Bn), 4.24 (t, J = 4.8 Hz, 2H,
d), 3.94 (t, J = 4.8 Hz, 2H, e), 3.90 (t, J = 5.8 Hz, 2H, f), 3.66 (t, J = 5.8
Hz, 2H, g); 13C NMR (100 MHz, CDCl3) δ191.8, 163.0,
162.2, 161.4, 135.2, 128.8, 128.6, 127.4, 106.7, 91.4, 89.5, 71.9, 70.9, 69.4,
69.3, 43.0; FT-IR (solid) 3034, 2926, 1634, 1566, 1501, 1449, 1417, 1386, 1296,
1218, 1204, 1120, 1090, 790, 740, 726, 699, 609, 563 cm-1.
Figure 2011162506
 （３）６-ベンジルオキシ-３-ブロモ-４-[２-(２-クロロエトキシ)エトキシ]-２-(４-メトキシベンジロキシ)ベンズアルデヒドの合成
６-ベンジルオキシ-３-ブロモ-４-[２-(２-クロロエトキシ)エトキシ]-２-ヒドロキシベンズアルデヒド(58.4
mg, 136 μmol) と炭酸セシウム (90.0 mg, 272 μmol) の DMF (700 μL) 溶液の中に、４-メトキシベンジルブロミド(22.0
μL, 163 μmol, 1.20 eq.) とヨウ化ナトリウム (8.00 mg, 54.4 μmol, 0.400 eq.) とアルゴン雰囲気室温下、加えた。室温下１２時間撹拌した後、反応溶液を水の酢酸エチル溶液に注いだ。水相を酢酸エチルで抽出し、得られた有機相を飽和食塩水で洗浄、硫酸マグネシウムで乾燥させた。減圧濃縮し、得られた残査をシリカゲルカラムクロマトグラフィーで精製（１５％酢酸エチル ヘキサン溶液）するこにより、目的とする臭素化体を白色固体として得た。(72.7
mg, 132 μmol, 97% yield)
TLC Rf 0.27 (hexane/ethyl acetate = 2/1); 1H
NMR (400 MHz, CDCl3) δ10.3 (s, 1H, a), 7.53 (d, J = 8.7 Hz, 2H, b),
7.34-7.46 (m, 5H, aromatic), 6.92 (d, J = 8.7 Hz, 2H, c), 6.45 (s, 1H, d), 5.20
(s, 2H, Bn), 4.97 (s, 2H, Bn), 4.21 (t, J = 4.8 Hz, 2H, e), 3.95 (t, J = 4.8
Hz, 2H, f), 3.90 (t, J = 5.8 Hz, 2H, g), 3.82 (s, 3H, h), 3.66 (t, J = 5.8 Hz,
2H, i); 13C NMR (100 MHz, CDCl3) δ187.0, 161.7, 161.0, 159.8,
159.2, 135.6, 130.6, 128.7, 128.3, 128.2, 127.0, 114.9, 113.8, 100.6, 95.1, 76.3,
71.8, 71.1, 69.3, 69.2, 55.2, 42.9; FT-IR (solid) 3034, 2932, 1634, 1615, 1512,
1456, 1417, 1386, 1297, 1247, 1218, 1118, 1033, 812, 744, 699, 608 cm-1.
Figure 2011162506
 （４）(E)-3-{6-ベンジルオキシ-3-ブロモ-4-[2-(2-クロロエトキシ)エトキシ]-2-(4-メトキシベンジルオキシ)フェニル}-1-[3,4,5-トリス(ベンジルオキシ)フェニル]-プロペ-2-エン-1-オンの合成
６-ベンジルオキシ-３-ブロモ-４-[２-(２-クロロエトキシ)エトキシ]-２-(４-メトキシベンジロキシ)ベンズアルデヒド(64.1
mg, 117 μmol, 1.00 eq.) のテトラヒドロフランTHF (800 μL) 溶液に3’,4’,5’-トリス(ベンジルオキシ)アセトフェノン(51.1
mg, 117 μmol, 1.00 eq.) とナトリウムメトキシド(19.0 mg, 350 μmol) をアルゴン雰囲気、室温下作用させた。室温下６時間反応させた後、反応溶液を水と酢酸エチルの混合溶液に注いだ。水相を酢酸エチルで抽出し、得られた有機相を飽和食塩水で洗浄、硫酸マグネシウムで乾燥させた。減圧濃縮し、得られた残査をシリカゲルカラムクロマトグラフィーで精製（１％酢酸エチル トルエン溶液）し、目的とする臭素化体を白色固体として得た。(114
mg, 118 μmol, quant.)
TLC Rf 0.49 (toluene/ethyl acetate = 9/1); 1H
NMR (400 MHz, CDCl3) δ8.22 (d, J = 15.9 Hz, 1H, a or b), 7.97 (d, J
= 15.9 Hz, 1H, a or b), 7.23-7.48 (m, 24H, aromatic), 6.84 (d, J = 8.7 Hz, 2H,
c), 6.50 (s, 1H, d), 5.20 (s, 2H, Bn), 5.11 (s, 2H, Bn), 4.93 (s, 4H, Bn), 4.84
(s, 2H, Bn), 4.22 (t, J = 4.8 Hz, 2H, e), 3.96 (t, J = 4.8 Hz, 2H, f), 3.92 (t,
J = 5.8 Hz, 2H, g), 3.68 (t, J = 5.8 Hz, 2H, h), 3.66 (s, 3H, i); 13C
NMR (100 MHz, CDCl3) δ189.6, 159.8, 159.1, 157.8, 157.4, 152.5,
142.2, 137.4, 136.6, 135.8, 135.3, 133.8, 130.7, 128.8, 128.5, 128.4x2, 128.1,
127.8, 127.5, 127.2, 123.5, 113.9, 113.4, 108.0, 100.5, 95.4, 75.3, 75.0, 71.8,
71.1, 71.0, 69.4, 69.3, 55.0, 42.9; FT-IR (solid) 3032, 2934, 1653, 1611, 1583,
1515, 1454, 1424, 1370, 1323, 1251, 1164, 1103, 1030, 851, 826, 738, 697 cm-1.
Figure 2011162506
 （５）3-{6-ベンジルオキシ-3-ブロモ-4-[2-(2-クロロエトキシ)エトキシ]-2-(4-メチルベンジルオキシ)フェニル}-1-[3,4,5-トリス(ベンジルオキシ)フェニル]-2-ヒドロキシ-3-メトキシプロパン-１オンの合成
(E)-3-{6-ベンジルオキシ-3-ブロモ-4-[2-(2-クロロエトキシ)エトキシ]-2-(4-メトキシベンジルオキシ)フェニル}-1-[3,4,5-トリス(ベンジルオキシ)フェニル]-プロペ-2-エン-1-オン
(114 mg, 118 μmol, 1.00 eq.) の塩化メチレン(1.75 mL) 溶液に３０％の過酸化水素水 (1.30 mL, 11.6
mmol), 3 M水酸化カリウム (580 μL) と硫酸水素テトラブチルアンモニウム (80.0 mg, 233 μmol, 2.00 eq.) を室温下加えた。室温下４８時間反応させた後、反応溶液を１０％チオ硫酸ナトリウム水溶液と酢酸エチルとの混合溶液に注いだ。水相を酢酸エチルで抽出し、得られた有機相を１０％チオ硫酸ナトリウム水溶液と飽和食塩水で洗浄、硫酸マグネシウムで乾燥させた。減圧濃縮し、得られた残査を次の反応に用いた。
得られた残査のメタノール (600 μL) と CH2Cl2
(600 μL) の混合溶液に触媒量のSc(OTf)3 (11.0 mg, 23.3 μmol) を室温下加えた。室温下３時間反応させた後、反応溶液を飽和炭酸水素ナトリウム水溶液と酢酸エチルの混合溶液に注いだ。水相を酢酸エチルで抽出し、得られた有機相を飽和食塩水で洗浄、硫酸マグネシウムで乾燥させた。減圧濃縮し、得られた残査をシリカゲルカラムクロマトグラフィーで精製（５％酢酸エチル トルエン溶液）し、目的とするヒドロキシケトンを白色固体として得た。
(74.3 mg, 73.0 μmol, 62% yield)
TLC Rf 0.48 (hexane/ethyl acetate = 1/1); 1H
NMR (400 MHz, CDCl3, mixture of diastereomers) δ7.60 (d, J = 8.7 Hz,
2H, a), 7.22-7.43 (m, 20H, aromatic), 6.99 (s, 2H, b), 6.88 (d, J = 8.7 Hz, 2H,
c), 6.15 (s, 1H, d), 5.84 (br t, 1H, J = 6.8, 7.7 Hz, e), 4.76-5.05 (m, 11H, f
and Bn), 3.91-4.00 (m, 2H, g), 3.77 (s, 3H, h or i), 3.70-3.76 (m, 4H, j and k),
3.49-3.57 (m, 2H, l), 3.39 (s, 3H, h or i); FT-IR (solid) 3481, 3033, 2932,
1674, 1611, 1587, 1515, 1455, 1428, 1372, 1332, 1250, 1168, 1101, 1030, 848, 827,
740, 698 cm-1.
Figure 2011162506
 （６）3-{6-ベンジルオキシ-3-ブロモ-4-[2-(2-クロロエトキシ)エトキシ]-2-(4-メトキシベンジルオキシ)フェニル}-1-[3,4,5-トリス(ベンジルオキシ)フェニル]-3-メトキシプロパン-1-オン-2-イル
3,4,5-トリス(ベンジルオキシ)安息香酸エステルの合成
3-{6-ベンジルオキシ-3-ブロモ-4-[2-(2-クロロエトキシ)エトキシ]-2-(4-メチルベンジルオキシ)フェニル}-1-[3,4,5-トリス(ベンジルオキシ)フェニル]-2-ヒドロキシ-3-メトキシプロパン-１オン(202
mg, 198 μmol) のピリジン溶液(1.50 mL)に3,4,5-トリス(ベンジルオキシ)安息香酸(00) (96.0 mg, 218 μmol)と
EDCI・HCl (57.0 mg, 297 μmol, 1.50 eq.) とDMAP (5.00 mg, 39.6 μmol, 0.200 eq.) を室温下加えた。室温下１２時間反応させた後、反応溶液を１M塩酸水溶液と酢酸エチルの混合溶液に注いだ。水相を酢酸エチルで抽出し、得られた有機相を１M塩酸水溶液、飽和食塩水で洗浄、硫酸マグネシウムで乾燥させた。減圧濃縮し、得られた残査をシリカゲルカラムクロマトグラフィーで精製（２％酢酸エチル トルエン溶液）し、目的とするエステルを白色固体として得た。(249
mg, 173 μmol, 87% yield)
TLC Rf 0.39 (hexane/ethyl acetate = 2/1); 1H
NMR (400 MHz, CDCl3, mixture of diastereomers) δ7.59 (d, J = 8.2 Hz,
2H, a), 7.11-7.52 (m, 37H, aromatic), 7.12 (s, 2H, b), 7.00 (d, J = 8.7 Hz, 1H,
c), 6.79 (d, J = 7.7 Hz, 1H, c), 6.15 (s, 1H, d), 5.43 (d, 1H, J = 9.2 Hz, e), 4.94-5.20
(m, 13H, f and Bn), 4.87 (d, Jgem = 11.6 Hz, 2H, Bn), 4.72 (d, Jgem
= 11.6 Hz, 2H, Bn), 3.85-3.98 (m, 2H, g), 3.70-3.75 (m, 4H, h and i), 3.68 (s,
3H, j or k), 3.52 (t, J = 5.8 Hz, 2H, l), 3.42 (s, 3H, j or k); FT-IR (solid)
3032, 2933, 1714, 1683, 1588, 1515, 1500, 1455, 1428, 1370, 1329, 1250, 1203, 1170,
1113, 1030, 849, 825, 738, 697 cm-1.
Figure 2011162506
 （７）シス-5-ベンジルオキシ-2-[3,4,5-トリス(ベンジルオキシ)フェニル]-7-[2-(2-クロロエトキシ)エトキシ]クロマン-3-イル3,4,5-トリス(ベンジルオキシ)安息香酸エステルの合成
3-{6-ベンジルオキシ-3-ブロモ-4-[2-(2-クロロエトキシ)エトキシ]-2-(4-メトキシベンジルオキシ)フェニル}-1-[3,4,5-トリス(ベンジルオキシ)フェニル]-3-メトキシプロパン-1-オン-2-イル
3,4,5-トリス(ベンジルオキシ)安息香酸エステル(128 mg, 88.9 μmol, 1.00 eq.) の 塩化メチレン(1.70 mL) 溶液に、トリエチルシランと(200
μL) トリフルオロ酢酸(100 μL) を氷冷下加えた。２時間反応させた後、反応溶液を飽和炭酸水素ナトリウム水溶液と酢酸エチルの混合溶液に注いだ。水相を酢酸エチルで抽出し、得られた有機相を飽和炭酸水素ナトリウム水溶液、飽和食塩水で洗浄、硫酸マグネシウムで乾燥させた。減圧濃縮し、得られた残査をシリカゲルカラムクロマトグラフィーで精製（２％酢酸エチル トルエン溶液）し、目的とするクロマンを白色固体として得た
(79.4 mg, 66.4 μmol, 75% yield).
TLC Rf 0.47 (toluene/ethyl acetate = 15/1); 1H
NMR (400 MHz, CDCl3) δ7.19-7.43 (m, 37H, aromatic), 6.73 (s, 2H, a),
6.31 (d, J = 1.9 Hz, 1H, b or c), 6.30 (d, J = 1.9 Hz, 1H, b or c), 5.67 (br s,
1H, d), 4.89-5.07 (m, 9H, e and Bn), 4.90 (s, 2H, Bn), 4.80 (d, Jgem
= 11.6 Hz, 2H, Bn), 4.68 (d, Jgem = 11.6 Hz, 2H, Bn), 4.11 (t, J = 4.8
Hz, 1H, f), 4.11 (t, J = 4.8 Hz, 1H, f), 3.85 (t, J = 4.8 Hz, 2H, g), 3.80 (t,
J = 5.8 Hz, 2H, h), 3.63 (t, J = 5.8 Hz, 2H, i), 3.12 (dd, Jgem =
17.9 Hz, J = 4.3 Hz, 1H, j), 3.06 (dd, Jgem = 17.9 Hz, J = 2.4 Hz, 1H,
j); FT-IR (solid) 3032, 2932, 1713, 1618, 1592, 1499, 1454, 1430, 1370, 1327, 1214,
1157, 1110, 1077, 1029, 842, 817, 737, 697 cm-1.
Figure 2011162506
 （８）シス-7-[2-(2-アジドエトキシ)エトキシ]-5-ベンジルオキシ-2-[3,4,5-トリス(ベンジルオキシ)フェニル]クロマン-3-イル3,4,5-トリス(ベンジルオキシ)安息香酸エステルの合成
シス-5-ベンジルオキシ-2-[3,4,5-トリス(ベンジルオキシ)フェニル]-7-[2-(2-クロロエトキシ)エトキシ]クロマン-3-イル3,4,5-トリス(ベンジルオキシ)安息香酸エステル(379
mg, 317 μmol, 1.00 eq.) の DMF (1.90 mL) 溶液ににアジ化ナトリウム(62.0 mg, 951 μmol, 3.00
eq.) と ヨウ化テトラブチルアンモニウム (60.0 mg, 158 μmol, 0.50 eq.) を室温下加えた。７０度で３０時間反応させた後、反応溶液を水と酢酸エチルの混合溶液に注いだ。水相を酢酸エチルで抽出し、得られた有機相を飽和食塩水で洗浄、硫酸マグネシウムで乾燥させた。減圧濃縮し、得られた残査をシリカゲルカラムクロマトグラフィーで精製（２％酢酸エチル トルエン溶液）し、目的とするアジ化物を白色固体として得た。(382
mg, 318 μmol, quant.)
TLC Rf 0.53 (toluene/ethyl acetate = 8/1); 1H
NMR (400 MHz, CDCl3) δ7.17-7.43 (m, 37H, aromatic), 6.73 (s, 2H, a),
6.31 (d, J = 1.9 Hz, 1H, b or c), 6.30 (d, J = 1.9 Hz, 1H, b or c), 5.66 (br s,
1H, d), 4.93-5.05 (m, 9H, e and Bn), 4.91 (s, 2H, Bn), 4.81 (d, Jgem
= 11.6 Hz, 2H, Bn), 4.68 (d, Jgem = 11.6 Hz, 2H, Bn), 4.11 (t, J = 4.8
Hz, 1H, f), 4.11 (t, J = 4.8 Hz, 1H, f), 3.83 (t, J = 4.8 Hz, 2H, g), 3.72 (t,
J = 5.3 Hz, 2H, h), 3.39 (t, J = 5.3 Hz, 2H, i), 3.12 (dd, Jgem =
17.9 Hz, J = 4.3 Hz, 1H, j), 3.05 (dd, Jgem = 17.9 Hz, J = 1.9 Hz, 1H,
j); FT-IR (solid) 3031, 2927, 2100, 1715, 1674, 1619, 1591, 1498, 1454, 1429,
1369, 1326, 1260, 1212, 1156, 1102, 1028, 843, 802, 734, 697 cm-1.
Figure 2011162506
 （９）シス-7-[2-(2-アセトアミドエトキシ)エトキシ]-5-ベンジルオキシ-2-[3,4,5-トリス(ベンジルオキシ)フェニル]クロマン-3-イル3,4,5-トリス(ベンジルオキシ)安息香酸エステルの合成
シス-7-[2-(2-アジドエトキシ)エトキシ]-5-ベンジルオキシ-2-[3,4,5-トリス(ベンジルオキシ)フェニル]クロマン-3-イル3,4,5-トリス(ベンジルオキシ)安息香酸エステル(54.4
mg, 45.2 μmol) のテトラヒドロフラン(500 μL) 溶液に、トリフェニルフォスフィン(13.0 mg, 49.8 μmol) を室温下加えた。６０度で１０時間反応させた後、水(3.00
μL, 181 μmol)を反応容器に加えた。さらに、１時間反応させた後、無水酢酸(17.0 μL, 181 μmol)を反応容器に加えた。さらに、２時間反応させた後、反応溶液を水と酢酸エチルの混合溶液に注いだ。水相を酢酸エチルで抽出し、得られた有機相を飽和食塩水で洗浄、硫酸マグネシウムで乾燥させた。減圧濃縮し、得られた残査をシリカゲルカラムクロマトグラフィーで精製（３０％酢酸エチル トルエン溶液）し、目的とするアミド体を白色固体として得た。(54.3
mg, 44.6 μmol, 99%)
TLC Rf 0.20 (hexane/ethyl acetate = 1/2); 1H
NMR (400 MHz, CDCl3) δ7.16-7.44 (m, 37H, aromatic), 6.73 (s, 2H, a),
6.31 (d, J = 1.9 Hz, 1H, b or c), 6.28 (d, J = 1.9 Hz, 1H, b or c), 5.88 (br s,
1H, d), 5.67 (br s, 1H, e), 4.96-5.06 (m, 9H, f and Bn), 4.91 (s, 2H, Bn), 4.81
(d, Jgem = 11.6 Hz, 2H, Bn), 4.69 (d, Jgem = 11.6 Hz, 2H,
Bn), 4.09 (t, J = 4.8 Hz, 2H, g), 3.79 (t, J = 4.8 Hz, 2H, h), 3.60 (t, J = 5.3
Hz, 2H, i), 3.46 (t, J = 5.3 Hz, 2H, j), 3.13 (dd, Jgem = 17.9 Hz, J
= 4.3 Hz, 1H, k), 3.06 (dd, Jgem = 17.9 Hz, J = 1.9 Hz, 1H, k), 1.92
(s, 3H, l)1.
Figure 2011162506
 （１０）シス-7-[2-(2-アセトアミドエトキシ)エトキシ]-5-ヒドロキシ-2-(3,4,5-トリヒドロキシフェニル)クロマン-3-イル 3,4,5-トリヒドロキシ安息香酸エステルの合成
H-Cube(registered trademark) （テーラズナノ社製）にPd(OH)2/C
CatCart を装填し、５０度に加温した。水素圧は20 barとした。シス-7-[2-(2-アセトアミドエトキシ)エトキシ]-5-ベンジルオキシ-2-[3,4,5-トリス(ベンジルオキシ)フェニル]クロマン-3-イル3,4,5-トリス(ベンジルオキシ)安息香酸エステル(43.9
mg, 36.0 μmol, 1.00 eq.) をメタノル/テトラヒドロフラン混合溶媒(1/1, 45.0 mL) に溶解させて、0.5 mL/minの流速で、
H-Cube(registered trademark) 内に流した。カラム内をメタノール(15.0 mL)で洗浄した。集めた溶液を減圧下濃縮し得られた残査を逆相のシリカゲルカラムクロマトグラフィーで精製することにより、目的とするクロマン誘導体を得た。
(17.1 mg, 29.1 μmol, 81% yield)
TLC Rf 0.43 (chloroform/methanol = 2/1); 1H
NMR (400 MHz, acetone-d6/D2O = 2/1) δ6.94 (s, 2H, a),
6.59 (s, 2H, b), 6.07 (d, J = 1.9 Hz, 1H, c or d), 6.04 (d, J = 1.9 Hz, 1H, c
or d), 5.36 (br s, 1H, e), 4.98 (s, 1H, f), 3.99 (br s, 2H, g), 3.72 (t, J =
4.3 Hz, 2H, h), 3.54 (t, J = 5.3 Hz, 2H, i), 3.29 (t, J = 5.3 Hz, 2H, j), 2.96
(dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H, k), 2.86 (d, Jgem =
17.9 Hz, 1H, k), 1.86 (s, 3H, l)13C NMR
(67.8 MHz, acetone-d6/D2O = 2/1) δ 172.9, 166.7, 158.8, 157.0, 156.3, 145.7,
145.5, 138.9, 132.7, 130.0, 120.7, 109.7, 106.4, 100.0, 95.6, 94.3, 77.7,
69.6x2, 69.5, 67.7, 39.5, 26.1, 22.3.
Figure 2011162506
 （１１）シス-7-[2-(2-アミノエトキシ)エトキシ]-5-ベンジルオキシ-2-[3,4,5-トリス(ベンジルオキシ)フェニル]クロマン-3-イル3,4,5-トリス(ベンジルオキシ)安息香酸エステルの合成
H-Cube(registered trademark) （テーラズナノ社製）にPd(OH)2/C
CatCart を装填し、５０度に加温した。水素圧は20 barとした。シス-7-[2-(2-アジドエトキシ)エトキシ]-5-ベンジルオキシ-2-[3,4,5-トリス(ベンジルオキシ)フェニル]クロマン-3-イル3,4,5-トリス(ベンジルオキシ)安息香酸エステル(105
mg, 86.9 μmol)をメタノル/テトラヒドロフラン混合溶媒(1/1, 50.0 mL) に溶解させて、0.5 mL/minの流速で、 H-Cube(registered
trademark) 内に流した。カラム内をメタノール(25.0 mL)で洗浄した。集めた溶液を減圧下濃縮し得られた残査を逆相のシリカゲルカラムクロマトグラフィーで精製することにより、目的とするクロマン誘導体を得た。(26.8
mg, 49.1 μmol, 57% yield)
TLC Rf 0.49 (methanol/H2O = 2/1,
reverse-phase); 1H NMR (400 MHz, acetone-d6/D2O
= 2/1) δ6.94 (s, 2H, a), 6.59 (s, 2H, b), 6.06 (d, J = 2.4 Hz, 1H, c or d),
6.03 (d, J = 2.4 Hz, 1H, c or d), 5.36 (br s, 1H, e), 4.98 (s, 1H, f), 4.03 (br
s, 2H, g), 3.80 (br t, J = 4.8 Hz, 2H, h), 3.77 (t, J = 5.3 Hz, 2H, i), 3.21
(t, J = 5.3 Hz, 2H, j), 2.96 (dd, Jgem = 17.9 Hz, J = 4.3 Hz, 1H, k),
2.86 (dd, Jgem = 17.9 Hz, J = 1.5 Hz, 1H, k) 13C NMR (100 MHz, acetone-d6/D2O = 2/1) δ 166.6, 158.8, 157.2, 156.5,
145.9, 145.6, 138.8, 132.8, 130.1, 121.0, 109.8, 106.4, 100.2, 95.6, 94.3,
77.9, 69.8, 69.7, 67.8, 67.2, 40.0, 26.2; FT-IR (solid)
3181, 2928, 1686, 1622, 1513, 1449, 1343, 1237, 1157, 1103, 1036, 874, 820, 768,
737, 667, 502 cm-1.
Figure 2011162506
 （１２）標識体の合成
Rhodamine RedTM-X succinimidyl
ester (1.50 mg, 1.95 μmol, 1.00 eq.) のアセトニトリル(90.0 μL) 水 (10.0 μL)溶液にシス-7-[2-(2-アミノエトキシ)エトキシ]-5-ベンジルオキシ-2-[3,4,5-トリス(ベンジルオキシ)フェニル]クロマン-3-イル3,4,5-トリス(ベンジルオキシ)安息香酸エステル(1.00
mg, 1.95 μmol, 1.00 eq.) を-２０度で加えた。
１０分間反応させた後、トリエチルアミン(0.400 μL, 2.93 μmol)を加え、徐々に０度まで昇温した。さらに１０分間反応させた後、反応溶液減圧化濃縮した。得られた残査をVARIAN
Bond ELUT(registered trademark) C18)と逆相のHPLC (Inertsil C18 ODS, 3 μm, 10 x 75
mm, 20 mL/min, UV detection at 254 nm, a linear gradient of 10% of aqueous
acetonitrile (0-1 min), 10-100% of aqueous acetonitrile (2-20 min), tR
10.3 min) で精製することにいより目的とする標識体を得た。(800 μg, 0.667 μmol, 36%)
TLC Rf 0.38 (methanol/H2O = 2/1,
reverse-phase); 1H NMR (400 MHz, acetone-d6/D2O
= 2/1) δ8.61 (d, J = 1.9 Hz, 1H, a), 8.02 (dd, J = 1.9, 8.2 Hz, 1H, b), 7.40
(d, J = 8.2 Hz, 1H, c), 7.14 (s, 2H, d), 6.98 (d, J = 7.2 Hz, 2H, e or f), 6.96
(d, J = 7.2 Hz, 2H, e or f), 6.88 (br s, 2H, g), 6.69 (s, 2H, h), 5.81 (d, J =
2.4 Hz, 1H, i or j), 5.79 (d, J = 2.4 Hz, 1H, i or j), 5.32 (br s, 1H, k), 4.99
(s, 1H, l), 3.48-3.68 (m, 6H, m, n and o), 3.04-3.09 (m, 4H, p and q), 2.80
(dd, Jgem = 17.4 Hz, J = 4.3 Hz, 1H, r), 2.71 (d, J = 2.4 Hz, 1H, r),
1.20-1.52 (m, 8H, s).
Figure 2011162506
本発明のエピガロカテキンガレート誘導体は、医薬に利用可能なので、製薬などの産業分野に利用可能である。

Claims (9)

  1. 一般式（Ｉ）
    Figure 2011162506
     〔式中、Ｘは疎水性基を表し、Ｒ１及びＲ２は同一又は異なって、置換基を有していてもよいフェニル基を表す。〕
    で表される化合物。
  2. 一般式（Ｉ）におけるＸが、１〜６個の不飽和結合を含んでもよく、また、酸素原子又は窒素原子を含んでもよい直鎖状又は分岐鎖状の炭化水素基であることを特徴とする請求項１に記載の化合物。
  3. 一般式（Ｉ）におけるＸが、置換基を有していてもよいアルキル基、置換基を有していてもよいアルケニル基、置換基を有していてもよいアルキニル基、置換基を有していてもよいアルコキシ基、置換基を有していてもよいアルケニルオキシ基、置換基を有していてもよいアルキニルオキシ基、置換基を有していてもよいアルコキシアルコキシ基、置換基を有していてもよいアルコキシアルコキシアルコキシ基、ハロゲン原子、又は水素原子であることを特徴とする請求項１に記載の化合物。
  4. 一般式（Ｉ）におけるＸが、メトキシ基又はエトキシ基であることを特徴とする請求項１に記載の化合物。
  5. 一般式（Ｉ）におけるＲ１及びＲ２が、同一又は異なって、ヒドロキシ基及び／又はメトキシ基を有するフェニル基であることを特徴とする請求項１乃至４のいずれか一項に記載の化合物。
  6. 一般式（Ｉ）におけるＲ１及びＲ２が、同一又は異なって、3,4,5-トリメトキシフェニル基、4-ヒドロキシ-3,5-ジメトキシフェニル基、3,5-ジヒドロキシ-4-メトキシフェニル基、又は3,4,5-トリヒドロキシフェニル基であることを特徴とする請求項１乃至４のいずれか一項に記載の化合物。
  7. 請求項１乃至６のいずれか一項に記載の化合物を含有することを特徴とする医薬組成物。
  8. 請求項１乃至６のいずれか一項に記載の化合物を含有することを特徴とする抗腫瘍剤。
  9. 請求項１乃至６のいずれか一項に記載の化合物を含有することを特徴とする抗アレルギー剤。
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07179489A (ja) * 1993-12-21 1995-07-18 Mitsui Norin Kk 新規ポリフェノール配糖体
JPH093089A (ja) * 1995-06-21 1997-01-07 Mitsui Norin Kk 新規ポリフェノール配糖体、その製造法およびその用途
CN1448395A (zh) * 2003-04-03 2003-10-15 浙江大学 抗氧化剂的egcg脂肪酸酯及其制备方法
JP2006510658A (ja) * 2002-12-06 2006-03-30 エスアールアイ インターナショナル 化学療法剤および化学予防剤としての緑茶ポリフェノールのアナログ
JP2008174507A (ja) * 2007-01-19 2008-07-31 Suntory Ltd フラボノイド類の配糖化方法

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JPH07179489A (ja) * 1993-12-21 1995-07-18 Mitsui Norin Kk 新規ポリフェノール配糖体
JPH093089A (ja) * 1995-06-21 1997-01-07 Mitsui Norin Kk 新規ポリフェノール配糖体、その製造法およびその用途
JP2006510658A (ja) * 2002-12-06 2006-03-30 エスアールアイ インターナショナル 化学療法剤および化学予防剤としての緑茶ポリフェノールのアナログ
CN1448395A (zh) * 2003-04-03 2003-10-15 浙江大学 抗氧化剂的egcg脂肪酸酯及其制备方法
JP2008174507A (ja) * 2007-01-19 2008-07-31 Suntory Ltd フラボノイド類の配糖化方法

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