Absolute stereochemistry of amphidinolide C: synthesis of C-1-C-10 and C-17-C-29 segments

Two of each diastereomers of the C-1-C-10 and C-17-C-29 segments of amphidinolide C (1) were synthesized. Comparing the ¹H NMR chemical shifts of its MTPA esters with those of linear methyl ester of 1, the absolute configurations at C-7, C-8, C-20, C-23, and C-24 in amphidinolide C (1) were confirmed to be all R.     

Synthesis of the C16-C28 spiroketal subunit of spongistatin 1 (altohyrtin A): the pyrone approach

The synthesis of the CD spiroketal fragment of spongistatin 1 (altohyrtin A) has been accomplished utilizing the addition of a metalated pyrone to an aldehyde and subsequent acid-catalyzed spirocyclization. A stereoselective hydrogenation and subsequent conformational inversion establish the C19 stereocenter and the axial-equatorial spiroketal center.     

Concise synthesis of the C-1-C-12 fragment of amphidinolides T1-T5

The C-1-C-12 segment of the amphidinolides T1-T5 has been synthesised in an efficient manner. The key transformations are highly diastereoselective rearrangement of an oxonium ylide, or metal-bound ylide equivalent, produced by intramolecular reaction of a copper carbenoid with an allylic ether, and macrocyclic fragment coupling by one-pot ring-closing metathesis and hydrogenation.     

A practical and efficient synthesis of the C-16-C-28 spiroketal fragment (CD) of the spongistatins

A practical and efficient route to the CD spiroketal (C-16-C-28) of the spongistatins is reported. Two stereocenters are introduced from chiral building blocks with the remainder introduced by substrate-controlled transformations. The key beta-keto-1,3-dithiane intermediate is generated by a dithiol conjugate addition to an ynone and the 1,3-dithiane unit in the C-ring plays a key role in the spiroketalization and subsequent epimerization. The synthesis requires 24 steps, with a longest linear sequence of 19 steps in an overall yield of 14.5% (for the longest linear sequence). [reaction: see text]     

熊果酸C-3,C-28位衍生物的合成及其抗肿瘤活性研究

以天然产物熊果酸为原料,经过氧化、酰化、酯化等反应合成了11个未见报道的熊果酸衍生物,其结构经过MS、1H NMR及元素分析确定。以氟尿嘧啶和吉非替尼为阳性对照药,经MTT法对A549和SGC-7901细胞进行初步体外抗肿瘤活性研究。结果表明,目标化合物对两种细胞株的抑制率均明显高于母体化合物,且化合物4b和5a的抑制效果高于阳性对照药,值得进一步研究。     

Synthesis of the ABCD and ABCDE ring systems of azaspiracid-1

The efficient syntheses of the ABCD ring system of the originally proposed structure of azaspiracid-1 and the ABCDE ring system of the revised structure of azaspiracid-1 containing the correct stereochemistry at C(6), C(10), C(13), C(14), C(16), C(17), C(19), C(21), C(22), C(24) and C(25) have been achieved.     

Synthesis of the C29-C44 portion of spongistatin 1 (altohyrtin A)

Two synthetic approaches to the C29-C44 portion of spongistatin 1 (altohyrtin A) have been developed. The key step of the first approach relies on the Claisen rearrangement of glucal 18 to provide ester 20a. This intermediate was advanced to silyl enol ether 30, which was coupled under Mukaiyama aldol conditions with aldehyde 3. Cyclization of this aldol adduct completed our first synthesis of the C29-C44 portion of spongistatin 1, requiring 25 total steps and occurring in 2.4% yield over the longest linear sequence (21 steps). We have also developed a second-generation approach based on the C-glycosidation of glucal 43. Through equilibration of the corresponding C-glycosides 49a/b and 50a/b the desired C-glycoside (50a) was obtained in good yield. Aldol condensation of this ketone provided cyclization precursor 67, which undergoes acid-catalyzed ketalization to close the E-ring of the spongistatins. An oxidation/reduction protocol was employed to set the C37 stereocenter. Protection of the C37 carbonol and selective unmasking of the C44 carbonol completed our second generation synthesis. This approach requires 27 steps and occurred in 13.2% yield over the longest linear sequence (18 steps).     

Synthesis of the C(2)-C(13) fragment (the A-B spiroketal unit) of spongistatin 1 (altohyrtin A): use of a common intermediate for the synthesis of both spongistatin spiroketals

[reaction: see text] A convergent synthesis of 14 corresponding to the A-B spiroketal core of spongistatin 1 has been accomplished via an iodo-spiroketalization reaction of glycal 9, which was synthesized in three steps from a late-stage intermediate used in our synthesis of the C-D spiroketal fragment of spongistatin 1. Elaboration of 14 to the A-B spiroketal 15 was accomplished in three steps.     

光学活性松干蚧性信息素C-8-C-13片断的合成

本文报道了从(S)-香茅醇合成化合物(2R)-3,5-dimethyl-hexan-1-o1(9), 即光学活性日本松干蚧性信息素C-8-C13片断, 共经九步反应, 总产率为57%。     

Synthesis of the ABCD fragment of gymnocin-B

A convergent synthesis of the ABCD fragment of gymnocin-B was accomplished. The tetracyclic ether ring system was synthesized by the construction of the BC ring system via the oxiranyl anion alkylation and ring expansion reaction, followed by the formation of the five-membered A-ring via a stereoselective radical cyclization reaction of a neopentyl-type iodide.     

Synthesis of the ABCD ring of gambierol

A fully functionalized ABCD ring moiety of gambierol, a marine polycyclic ether toxin, was synthesized by the use of the oxiranyl anion strategy and reductive cycloetherification of a beta,delta-dihydroxy ketone.     

Synthesis of new 1-C-(2-furyl)-and 3-C-(2-furyl)-hexopyranosides and 3-C-(2-furyl)-daunorubicin analogs

Summary Reaction of furan with 3,4-di-O-acetyl-L-rhamnal (1) afforded a mixture of epimeric 3-C-(2-furyl) glycals3 and4 and 1-C-(2-furyl)-hex-2-enopyranoses5 and6. Glycals3 and4 were transformed to 2-deoxy-glycosides9–13 and 3-deamino-3-C-(2-furyl)daunorubicines15 and16. Hex-2-enopyranosyl5 wascis hydroxylated with osmium tetroxide/N-methylmorpholine N-oxide to C-glycoside14.On leave from Pharmaceutical Research Institute, Warsaw, Poland     

Diastereoselective synthesis of the C(17)-C(28) fragment (the C-D spiroketal unit) of spongistatin 1 (altohyrtin A) via a kinetically controlled iodo-spiroketalization reaction

[reaction: see text] A convergent and stereocontrolled synthesis of spiroketal 15 corresponding to the C-D fragment of spongistatin 1 has been accomplished by a sequence utilizing a kinetically controlled intramolecular iodo-spiroketalization of glycal 2, which in turn was synthesized via a ring-closing metathesis reaction.     

Synthesis of the monocyclic nonaromatic C-1 to C-10 fragments of the milbemycins and avermectins.

The efficient synthesis of C-1 to C-10 monocyclic nonaromatic fragments of the milbemycins and avermectins has been achieved, in which the key step involved the stereoselective addition of 2-lithio-4-phenylthiobut-1-ene to a 3-hydroxycyclohexanone derivative.     

Synthesis of 2-C- and 3-C-Aryl Pyranosides

Abstract

Lithium diphenylcuprate treatment of methyl 2,3-anhydro-4,6-O-benzylidene-D-pyranosides in which the anomeric substituent and the three-membered rings are cis oriented furnished the expected trans-diaxial opening products. When the relationship between the anomeric group and the epoxide was trans, the same experimental conditions led only to recovered starting material. Cyano cuprates of the type R₂CuCNLi₂ added stereoselectively to carbohydrate ketones at C-2 and C-3 from the opposite side relative to the anomeric substituent.     

Synthesis of 1-14C-17-iodoheptadecanoic acid

1,16-Diiodohexadecane was obtained by reaction of 1,16-hexadecanediol and potassium iodide. The¹⁴C-label was introduced into the 1,16-diiodohexadecan using a substitution reaction which replaced one of the terminal iodine with¹⁴C-cyanide. Hydrolysis and HPLC purification of 1-¹⁴C-17-iodoheptadecanoic acid yielded a product with a radiochemical yield of 17% and a specific activity of approx. 1850 MBq mol^–1.