Synthetic approaches to syn-diol containing biologically active compounds /

The deoxy derivative of pancratistatin 1.10 was prepared in good yield through the use of a [4+2] Diels-Alder cycloaddition and Bischler-Napieralski cyclization approach. The Bischler-Napieralski cyclization was shown to yield two additional side products 2.9, 2.10, however, under slightly modified hydrolysis conditions, the tetracyclic product 2.11 was obtained exclusively in greater than 84% yield. Initial screening of the di-hydroxylatgd derivative, and the other complementary pair analogue 1.10' previously prepared in our laboratories gave interesting results. Both of these compounds were shown to exhibit cytostatic activity; the mono-alcohol was marginally active while the di-hydroxylated analogue proved to be more potent although one to two magnitudes less potent than pancratistatin itself Human tumour cell line assay results indicated that the di-hydroxylated derivative exhibited selective cytotoxic inhibition in the following cell lines: non-small cell lung cancer line NCI-H226 (ED50 - 0.65 ^g/mL), leukemia cell lines CCRF-CEM (ED30 = 0.55 Hg/mL) and HL-60(TB) (ED50 = 0.89^ig/mL). Our results demonstrated that the pharmacophore is not a mono-alcohol, and that the minimum pharmacophore contains the hydroxyl group at the C4 position in addition to either, or both, of the hydroxyl groups present at C2 and C3.' The minimum pharmacophore has been narrowed to only three possibilities which are current synthetic targets in several research groups. The controlled Grignard addition to the tartaric acid derived bis-Weinreb amide 1.25 afforded a direct entry to a host of 1,4-diflferentiated tartaric acid derived intermediates (2.12-2.18). This potentially usefiil methodology was demonstrated through the efficient synthesis of the naturally occurring lactone 2.23, which bears the inherent syn-dio\ subunit. Based on this result, a similar approach to the synthesis of syn-dio\ bearing natural products looks very promising? A direct 2,3-diol desymmetrization method using TIPS-triflate was shown to be effective on the selective differentiation of Z,-methyl tartrate (and diisopropyl tartrate). The mono-silyl-protected intermediates 2.31 also proved to be useful when they were selectively differentiated at the 1,4-carboxyl position (2.35, 2.36) through the use of a borohydride reducing agent. Furthermore, the mono-silyl-protected derivative underwent periodate cleavage affording two synthetically useful a,P-unsaturated esters 2.43, 2.44, with one of esters being obtained via a silyl-migration method.''

HG 188.60-188.70 Thin Section

Dark brown sediment with mainly small grains. Clasts are sub-angular. Abundant in lineations, grain stacking, and minor grain crushing. Lineations are oriented in multiple directions.

HG 226.50-226.60 Thin Section

Dark brown sediment with manly small sized clasts. Some medium and large clasts also present. Clasts range from sub-angular to sub-rounded. Lineations can be seen throughout the sample. Minor patches of clay/organic rich domains can also be seen as well as minor grain stacking.

HG 253.60-253.70

Coarse grained sample, with generally medium sized clasts. Clasts were sub-angular to sub-rounded. Many rotation structures, as well as large amounts edge-to-edge grain crushing are also present.

HG 384.60-384.70

Dark brown sediment with scattered amounts of small clasts and medium clasts as well. Clast shape ranges from sub-angular to sub-rounded. Lineations and water escape structures are abundant in this sample.

HG 393.60-393.85

Brown sediment with clasts that range from small to large. The clast shape ranges from angular to sub-rounded. Lineations and water escape structures are present. Grain crushing and minor amounts of rotation are also present.

HG 421.50-421.60

Light brown sediment with clasts that range from small to large in size. The clast shape ranges from sub-angular to sub-rounded. Lineations and rotation structures are abundant in this sample. Edge-to-edge grain crushing is present as well. There are areas of light and dark sediment throughout the sample. A few comet structures can also be seen.

HG 445.60-445.75

Coarse grained, light brown sample with clasts ranging from small to medium in size. The clast shape ranges from sub-angular to sub-rounded. Lineations were abundant throughout the sample. A few comet structures were also found.

HG 2.60-2.70

Brown sediment clasts ranging from small to large in size. Clasts range from sub-angular to sub-rounded in shape. Comet structures and grain crushing are commonly seen in this sample. Lineations and a few rotation structures can also be seen.

HG 29.60-29.80

Brown sediment with clasts that range from small to large. The clast shape ranges from angular to sub-rounded. The sample is abundant in necking and rotation structures. Minor edge-to-edge grain crushing can also be seen.

HG 75.45-75.60

Dark brown sediment with clasts ranging from small to medium in size. The clast shape ranges from angular to sub-rounded. Lineations are commonly seen throughout the sample. Grain crushing/stacking can also be seen along with varying amounts of rotation structures and comet structures.

HG 109.60-109.70

Dark brown sediment with clasts ranging from small to medium in size. Clast shape ranges from angular to sub-rounded. Lineations and comet structures are abundant. Some grain crushing and rotation structures can also be seen.

HG 114.60-114.70

Brown sediment with clasts ranging from small to medium in size. Clast shape ranges from angular to sub-rounded. Lineations and rotation structures are common throughout this sample. Some comet structures and grain crushing can also be seen throughout in minor amounts.

HG 129.50-129.60

Brown sediment with multiple domains. There are two finer grained domains that contain a few small clasts. These two can be distinguished based on the abundance of clay material(darker brown). The coarse grained sediment contains clasts ranging from small to medium in size, and angular to sub-rounded in shape. This domain contains lineations, rotation structures, comet structures, and some edge-to-edge grain crushing.