nanaomycin D | 60325-08-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异色满醌
• 英文名称: nanaomycin D
• 英文别名: (11S,15S,17S)-4-hydroxy-17-methyl-12,16-dioxatetracyclo[8.7.0.03,8.011,15]heptadeca-1(10),3(8),4,6-tetraene-2,9,13-trione
• CAS: 60325-08-8
• 化学式: C₁₆H₁₂O₆
• 分子量: 300.268
• InChiKey: XUWPJKDMEZSVTP-XMBDNQPKSA-N

物化性质

• 熔点：
  170-173 °C
• 沸点：
  624.5±55.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  nanaomycin D 在 platinum(IV) oxide 氢气 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以98%的产率得到2-((1S,3R)-9-hydroxy-1-methyl-5,10-dioxo-3,4,5,10-tetrahydro-1H-benzo[g]isochromen-3-yl)acetic acid
  参考文献：
  名称：

  纳奈霉素及其对映异构体卡拉芬净的对映发散全合成

  摘要：

  第一个，吡喃萘醌抗生素，nanaomycins D 和 A 及其对映异构体，kalafungin 和 4-deoxykalafunginic 酸的对映特异性全合成是通过来自常见光学活性中间体 (1S,3RS,4S)-3 的“对映发散”策略描述的， 4-dihydro-5,9,10-trimethoxy-1-methyl-1H-naphtho[2,3-c]pyran-3,4-diol，由L-鼠李糖通过4-甲氧基-3缩合得到(苯基磺酰基)-1(3H)-异苯并呋喃酮和甲基 3,4,6-三脱氧-α-L-甘油-己基-3-烯吡喃糖苷-2-酮糖。

  DOI：

  10.1246/bcsj.58.1699
• 作为产物：
  描述：

  1-(1,4,5-Trimethoxynaphthalen-2-yl)prop-2-enyl acetate 在 tris(dibenzylideneacetone)dipalladium (0) ammonium cerium(IV) nitrate 、 三氟化硼乙醚 、 三溴化硼 、 N,N-二异丙基乙胺 、 三苯基膦 、 sodium bromide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 58.67h， 生成 nanaomycin D
  参考文献：
  名称：

  Efficient Synthesis of (+)-Kalafungin and (-)-Nanaomycin D by Asymmetric Dihydroxylation, Oxa-Pictet-Spengler Cyclization, and H₂SO₄-Mediated Isomerization

  摘要：

  通过 11 个步骤从 1,5-萘二醇（13）合成了吡喃萘醌类抗生素和抗肿瘤药物 (+)-kalafungin (1) 和 (-)-nanaomycin D (3 = ent-1)。这两种化合物的立体选择性很高：1 的非对映选择性为 99.5%，3 的非对映选择性为 98.5%。δ,δ-不饱和酯 9 的不对称二羟基化实现了对映体控制。在最后一步，通过在 H2SO4 中几乎完全的外延化反应实现了非对映控制。

  DOI：

  10.1055/s-2005-868505

文献信息

• Stereoselective Synthesis of Kalafungin Based on CuI‐Catalyzed Tandem Reactions of Arylethynes Containing an Ortho‐(1‐Hydroxyethyl) Substituent with Alkyl Diazoacetates
  作者：Xiaoqing Song、Ruizhi Wang、Liang Shi、Tianlong Luo、Zhiyu Gao、Li Ren、Wenming Zhou、Hong‐Dong Hao

  DOI：10.1002/adsc.202100589

  日期：2021.9.21

  An isochromene synthesis is developed utilizing a cascade reaction involving a CuI catalyzed coupling reaction between an alkyne and diazoacetate followed by allenoate isomerization and subsequent oxa-Michael addition. The cascade sequence was also demonstrated for the synthesis of naphthalenes. Furthermore, the methodology developed herein was applied toward a stereoselective synthesis of pyranonaphthoquinone

  异色烯合成是利用级联反应开发的，该反应涉及炔烃和重氮乙酸酯之间的 CuI 催化偶联反应，然后是烯丙酸酯异构化和随后的氧杂-迈克尔加成。级联序列也被证明用于合成萘。此外，本文开发的方法应用于吡喃萘醌卡拉芬净的立体选择性合成。
• Unexpected Regioselectivity in the Synthesis of Pyranonaphthoquinone via the Diels−Alder Reaction
  作者：Yi Cui、Hao Jiang、Zhengtao Li、Na Wu、Zhen Yang、Junmin Quan

  DOI：10.1021/ol901902v

  日期：2009.10.15

  ylsilane 2 are explored by both computations and experiments. The regioselectivity is controlled by the electrostatic interaction of the lactone ring-oxygen and the vicinal quinone oxygen on the transition structure, which can be tuned by the terminal methyl group of the butadienes.

  通过计算和实验探索了吡喃醌1与（4,4-二甲氧基丁1,3-二烯-2-基氧基）三甲基硅烷2的Diels-Alder反应中异常的区域选择性。区域选择性由过渡结构上的内酯环-氧和邻位醌氧的静电相互作用控制，该相互作用可通过丁二烯的末端甲基进行调节。
• Synthesis of 8-Bromokalafungin as an Intermediate for the Preparation of C-Glycoside Derivatives
  作者：Margaret A. Brimble、Michael R. Nairn、Hishani Prabaharan、Nathan B. Walters

  DOI：10.1071/c97018

  日期：——

  The preparation of 8-bromokalafungin (20) which is a key intermediate for the synthesis of C-glycoside containing pyranonaphthoquinone antibiotics related to medermycin (6) is described. Although attempts to selectively monobrominate kalafungin (1) at C8 were unsuccessful, 8,10-dibromokalafungin (21) was prepared by using excess N-bromosuccinimide in chloroform. Selective bromination at C6 on a naphthalene ring was achieved upon treatment of naphthol (9) with N-bromosuccinimide (1 equiv.). Conversion of naphthol (9) into naphthoquinone (15) was effected by methylation, Baeyer–Villiger oxidation, acetylation via a Fries rearrangement and oxidation with ceric ammonium nitrate. Conversion of the 7-bromo quinone (15) into 8-bromokalafungin (20) proceeded through subsequent addition of 2-trimethylsilyloxyfuran (16) followed by oxidative rearrangement of the resultant furonaphthofuran (17) to furonaphthopyran (18). After reduction of the lactol (18) to cis ether (19), demethylation and epimerization at C5 with boron tribromide afforded 8-bromokalafungin (20). 8-Bromokalafungin (20) failed to undergo Pd(0)-mediated cross-coupling reactions with the stannyl glucal (22).

  8-bromokalafungin (20)是合成含吡喃萘醌的 C-糖苷的关键中间体。 8-bromokalafungin (20) 的制备方法。 8-bromokalafungin (20) 的制备方法。虽然试图 在 C8 处选择性地单溴化卡拉非菌素（1）的尝试并不成功、 通过使用过量的 在氯仿中使用过量的 N-溴代丁二酰亚胺制备出了 8,10-二溴卡拉非因（21）。选择性溴化 用 N-溴琥珀酰亚胺处理萘酚（9）时，在萘环 C6 处实现了选择性溴化。 N-溴代丁二酰亚胺（1 个等量物）。萘酚 (9) 通过甲基化作用转化为萘醌 (15)、 萘酚 (9) 通过甲基化、拜尔-维利格氧化、通过弗里斯重排进行乙酰化和 硝酸铈铵氧化。将 7-溴醌 (15) 转化为 8-bromokalafungin (20)。 2-三甲基硅氧基呋喃（16），然后将生成的呋喃萘醌氧化重排 呋喃（17）氧化重排为呋喃并吡喃（18）。将 内酯（18）还原成顺式醚（19）后，用三溴化硼在 C5 处进行去甲基化和表 三溴化硼进行脱甲基和 C5 处的环化反应，得到 8-溴木犀草素（20）。8-溴卡拉芬净（20） 未能发生钯（0）介导的与丹宁基 葡萄糖醛（22）发生交叉偶联反应。
• Direct Total Syntheses of Frenolicin B and Kalafungin via Highly Regioselective Diels-Alder Reactions
  作者：George A. Kraus、Jun Li、Mark S. Gordon、Jan H. Jensen

  DOI：10.1021/jo00110a017

  日期：1995.3

  Frenolicin B, an anticoccidial agent, has been synthesized in six steps from ketone 3. Racemic kalafungin, an antifungal agent, has been synthesized in five steps. The key step in both syntheses, a regioselective Diels-Alder reaction, proceeds with complete regiocontrol and in excellent yield. One rationale for the remarkable stereocontrol is that the lactone ring induces ring-puckering in the quinone subunit which, in consort with electrostatic repulsion, contributes to the regioselectivity.
• General Enantiospecific Route to Isochromanquinones. Synthesis of (-)-Nanaomycin D
  作者：Michael P. Winters、Michael Stranberg、Harold W. Moore

  DOI：10.1021/jo00104a004

  日期：1994.12

  A general enantiospecific synthesis of isochromanquinones is presented. This entails an efficient synthesis of (3aS, 5S, 7aR)-7-bromo-3,3a,5,7a-tetrahydro-5-methyl-2H-furo[3,2-b]pyran-2-one (12) and ultimately the lithium agent 15 from commercially available L-rhamnose. Addition of 15 to the appropriate cyclobutenedione followed by thermolysis of the resulting cyclobutenone leads to the isochromanquinones 16a-c. In an analogous fashion the naturally occurring product, (-)-nanaomycin D, was synthesized. In addition, new methodology involving the ring expansion of iminocyclobutenones to aminophenols was discovered.