C1-C13 Fragment Research Articles

Stereoselective synthesis of C1–C12 fragment of amphotericin B

An efficient synthesis of C1–C12 fragment of amphotericin B is described. The synthesis is based on asymmetric dihydroxylation and cross-metathesis reactions.

Application of oxetane ring opening toward stereoselective synthesis of zincophorin fragment

A stereoselective synthesis of the C1–C11 fragment of zincophorin was achieved by using an intramolecular oxetane ring opening reaction as the key step. The oxetane moiety was synthesized by employing a desymmetrization protocol developed at our group and a non-Evans syn aldol as the key steps toward the synthesis.

Total synthesis of reblastatin: convenient preparation of coupling partners and scaled assembly

Potentially scalable total synthesis of reblastatin was achieved based on Panek's previous study. Novel and convenient synthetic routes were developed for the known C8–C20 and C1–C7 coupling partners. The challenging C8–C20 fragment was prepared from TBS protected (S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (6) in nine steps (20% overall yield), and the C1–C7 fragment was synthesized from commercially available 3,4,6-tri-O-acetyl-d-glucal (9) in eight steps (35% overall yield). On a larger scale, Panek's eight-step assembly of the target molecule from the two partners was also slightly modified, giving 45 mg reblastatin (19% overall yield) in the first batch synthesis. Notable feature of our study is the settlement of the C14 chirality through a diastereoselective α-alkylation of 6 followed by a three-step full reduction of the lactone carboxyl, making vastly available 6 a universally applicable C11–C14 synthon for benzenoid/benzoquinone ansamycins.

ChemInform Abstract: Novel Iodine Catalyzed Diastereoselective Synthesis of trans‐2,6‐Disubstituted Tetrahydro‐2H‐pyrans: Synthesis of C1—C13 Fragment of Bistramide‐A.

AbstractTrans‐2,6‐substituted 2‐allylated pyrans are stereoselectively prepared by iodine catalyzed allylation of the corresponding tetrahydro‐2H‐pyranols.

A unified strategy for the synthesis of the C1–C14 fragment of marinolic acids, mupirocins, pseudomonic acids and thiomarinols: total synthesis of pseudomonic acid methyl monate C

A flexible stereoselective approach to the common C1-C14 skeleton present in natural products of the pseudomonic acid family is described. The strategy has been extended and the total synthesis of pseudomonic acid methyl monate C was achieved. The key synthetic reactions utilized include Achmatowicz rearrangement, Johnson-Claisen rearrangement, Julia-Kocienski olefination, and Horner-Wadsworth-Emmons olefination reaction.

Stereocontrolled Synthesis of the C1-C7 Fragment of Enigmazole A

Stereocontrolled Synthesis of the C1-C7 Fragment of Enigmazole A

Cross-Metathesis Approach for Stereocontrolled Synthesis of the C1–C15 Fragment of Rhizopodin

The C1–C15 fragment of rhizopodin was synthesized through either Suzuki coupling reaction of vinyl iodide and vinyl boronate or cross-metathesis of a terminal olefin and a diene adduct in the presence of Hoveyda–Grubbs II catalyst.

Novel iodine catalyzed diastereoselective synthesis of trans-2,6-disubstituted tetrahydro-2H-pyrans: synthesis of C1–C13 fragment of bistramide-A

A new method for the stereoselective synthesis of trans 2.6-disubstituted tetrahydro-2H-pyrans has been developed involving iodine catalyzed allylation of tetrahydro-2H-pyranol with excellent trans selectivity. The method was also applied toward the construction of C1–C13 fragment of bistramide-A in 11 steps with 21.4% overall yield.

Synthesis of the C1–C15 fragment of palmerolide A via protecting group dependent RCM reaction

Abstract The steric effect of protecting groups on the outcome of the ring-closing metathesis reaction has been studied for the construction of key 13-membered macrolactone. The protocol has been successfully utilized for the synthesis of C1–C15 fragment of palmerolide A in a highly convergent and concise manner.

Syntheses of the C1–C14 and C15–C25 Fragments of Amphidinolide C

Divergent syntheses of the C1-C14 and C15-C25 fragments of amphidinolide C have been achieved. The synthesis of the C15-C25 fragment featured cobalt-catalyzed modified Mukaiyama aerobic alkenol cyclization and sulfur-directed regiocontrolled Wacker oxidation of an internal alkene. The C1-C14 fragment was established by alkenyllithium addition to an aldehyde followed by a challenging olefination of a highly inert C9 ketone.

Process Development of Halaven®: Synthesis of the C1-C13 Fragment from d-(-)-Gulono-1,4-lactone

Process Development of Halaven®: Synthesis of the C1-C13 Fragment from d-(-)-Gulono-1,4-lactone

Relative Stereochemical Determination and Synthesis of the C17–C25 δ-Lactone Fragment of Hemicalide

Hemicalide is a novel marine metabolite polyketide distinguished by a unique mechanism of action. Because of insufficient quantities of purified material, this natural product has evaded complete stereochemical assignments. Recently, we have determined the relative stereochemistry of the C8-C13 hexad by synthesizing the C1-C13 fragment. Presently, we report the assignment of the C17-C25 δ-lactone fragment. NMR analysis of authentic hemicalide along with a computational conformation study allowed us to reduce the number of putative relative isomers from 16 to 4. Concise syntheses of the four candidate diastereomers were achieved using a common strategy based on a Dias aldehyde allylation reaction, an intramolecular Horner-Wadsworth-Emmons olefination, and a dihydroxylation reaction. Finally, thorough NMR comparisons enabled us to deduce the relative stereochemistry of the C1-C17 fragment with high certainty.

ChemInform Abstract: Stereoselective Synthesis of the C1—C16 Fragment (VII) of Goniodomin A

Abstractinvolving the Stille‐type coupling of thioester (II) with vinylstannane (III) and spiroacetalization of diol mixture (V)/(VI) as the key steps

Process Development of Halaven®: Synthesis of the C1-C13 Fragment from d-(-)-Gulono-1,4-lactone

A 12-step kilogram-scale synthesis of the C1–C13 fragment, common to halichondrin B and the totally synthetic analogue Halaven® (E7389, INN eribulin mesylate), is described. The synthesis features four crystalline intermediates which facilitates throughput, and enhances quality control of all stereogenic centers in the title compound.

Synthesis of the C1–C15 fragment of elaiolide

The synthesis of the C1–C15 fragment of elaiolide was achieved by successfully utilizing the desymmetrization strategy, zirconium catalyzed C–C bond formation and double stereodifferentiating aldol reactions.

A stereoselective approach for the southeast segment (C1–C16) of (+)-sorangicin A

The stereoselective protective group-free synthesis of the C1-C16 fragment of (+)-sorangicin A consisting of a dihydropyran subunit with a chiral alkyl substituent is achieved. The synthesis of the 4-stereogenic centered subunit involved key reactions such as Noyori asymmetric transfer hydrogenation, Achmatowicz oxidative rearrangement, and highly diastereoselective allylation of the Achmatowicz adduct.

An iterative, facile stereoselective synthesis of C1-C11 fragment of borrelidin via enzymatic desymmetrization strategy

A highly stereoselective and general method for the synthesis of the C1-C11 fragment of borrelidin has been achieved. The main feature of our synthetic route is enzymatic desymmetrization to create two methyl bearing chiral centres, use of Evans auxiliary to introduce two other methyl groups and creation of C3 stereocentre by regioselective opening of an epoxide arising from Sharpless epoxidation protocol. The synthesis of the C1-C11 subunit was achieved in gram scale by a linear synthetic sequence in an overall yield of 18.4%.

Synthesis of a C1–C11 fragment of Zincophorin using planar chiral, neutral π-allyl iron complexes

A key step in the synthesis of a C1-C11 fragment of the ionophore antibiotic Zincophorin involves the addition of an α-alkoxyalkylcopper(I) reagent to a planar chiral, neutral π-allyl iron complex. The key allylic alkylation reaction is highly regio- and stereoselective with addition taking place at the γ-position anti to the metal centre.

Enantioselective synthesis of the C1-C11 fragment of tedanolide C.

A convergent synthesis of the protected C(1)-C(11) fragment 6 of the targeted enantiomer of tedanolide C is described. The key step of the synthesis is the Felkin-Ahn addition of vinyl iodide 7 to aldehyde 8 that proceeds in 80% yield with 4:1 diastereoselectivity.

Stereoselective Synthesis of the C1–C16 Fragment of Goniodomin A

Abstract Stereoselective synthesis of the C1–C16 fragment of the antifungal marine polyether macrolide goniodomin A is described. A Stille-type coupling of organostannanes and thioesters was exploited as the key carbon–carbon bond-forming process, namely for the formation of the C7–C8 and C11–C12 bonds. Construction of the spiroacetal domain via acid-catalyzed acetalization of a triol-enone 30 unexpectedly provided a mixture of natural 11S spiroacetal 2, unnatural 11R spiroacetal 32, and constitutional isomer 33. Fortunately, it was eventually found that protection of the C5 hydroxy group as its acetate facilitated the isolation of natural 11S isomer 47 via acid-catalyzed equilibration of unnatural 11R isomer 48 and avoided the formation of a constitutional isomer, thereby increasing the efficacy of the spiroacetalization process.